PHARMACEUTICAL EDUCATION

NIPER JEE 2011 paper

2012-02-02T22:17:00.001-08:00

Niper 2011 Paper

1)Plantago…seed,root,bark
2)Aegle marmelose family…Rutaceae,malvaceae
3)competitive inhibitor….increase substate level
4)Short actin Drug….propofol,thiopental
5)Morphine discovered in…1904,1820
6)kaolin…hydrated Al silicate,hydrated Mg silicate
7)Controlled Drug delivery sym which is usd…HPMC,phalate,DCP
8)morphine…analgesic,anticonvulsant,both,none
9)Dry heat soln filling…..Dry heat sterilizatn,moist heat,aseptic fillin
10)D-glyceraldehyde configuration…S,R,RS
11)D-threose,D-erythrose,Lthreose related ques
12)erythrose and threose are???......distereoisomers,epimers,Enantiomers
13)Kaya skin clinic by company…ITC,
14)Indian institute of homeopathy??...Kolkata,jaipur,Bombay
15)preterm delivery vch drug use??..Atosiben,sulfoprostone,oxytocin
16)Psoralia obtaind from..Apigenin,Umbeliferone
17)Vch of following obtaind frm marine????...pralidoxime,heparin,both,none
18)Heparin ant..Ans protamine sulphate
19) 8 hrs…40km/hr…60 km/hr….ans 400
20)S is taller than a,a is taller than b lyk ques
21)witting reaction…phosprous
22)Cardinolide…butanone,batanedione,butanolides
23)Propranolol chemical name
24)Ehrlich reagent…P-dimethyl benzaldehyde
25)BCE;FGI:…
26)i-methyl benzoate..ii..phenyl acetate,,iii Acetophenone..IR range,,i=ii>iii,i>ii>iii
27)NH gives peak at..780,1100,3400
28)Stat phase nd mobile phase in RP chromatography..
29)Intracutaneous Max vol….0.01,0.1,0.2,1
30)BCCI memb
31)Fecl3+catechol colour….purple,red,green
32)Third generation sulphonamide usd in diabetis…Repaglinide,Glimipride,metformin,phenformin
33)Endothelial cell present in..Blood,lung,
34)Vch tissue has slowest equilibrium drug in blood…brain,fat,muscle,liver
35)platelets obtained from?? Ans megakaryotes
36)h2o nd D2O attack…Elimination,SN2,SN1
37)Walden inversion….SN1,SN2,E1,E2
38)Blood pH..7.4
39)Crystalline str related ques…
40)Vch method best suit to convert amorphous to crystalline….micronization,spray drying,any of above
41)emulsion measurement not by….electric charge,light scaterin,
42)DLVO theory…
43)microemulsion globule size…
44)beta galactosidase…SDS page…Band…2,1,,,,1,2….11….22…
45)PCR sequence
46)vch of following is not diuretic???..triamterine.indapamide,furosemide
47)Vch f followinnot active??...Allene,biphenyl.meso tartaric,None…
48)Gossypol…..not chiral,restricted rotation..
49)Eucalyptos oil ctn…geraneol,1-8 cineole,
50)AU..Bz..Cy….ans DX
51)20student height 120,10 student height 100…Avg height ans 105
52)Sania mirza….
53)German company take over.teva,sanofi,Pfizer..
54)book..fatima…
55)WOF used in tretmnt of diarrohea…erythromycin,domperidone,cisapride nd one new drug
56)cycloaddition..dial alder reactn
57)thinamerin dehydrogenation produce….antracene,naphthalene…
58)synthetic Ach better than natural Ach….due to slwer hydrolysis…
59)If increase dose f salbutamol,decrease actn by…downregulation,upregulatin…
60)vch is permeable..polystrene…
61)bond energy…..
62)Tymoleptics??
63)Max absorption from cell memb….ionizdform,unionized form…
64)WOf is not sede efeect of phenothiazine???
65)WOFis not hepatotoxic??..rifampicin,isoniazid,ethambuto,streptomycin
66)Inhibit Aminotranferase nd 30S….tetracycline,macrolide
67)Inhibitr f 50 s ….macrlide,tetracycline
68)synonym…Graphics
69)Pictorial
70)magnaminous
71)Rebate
72)WOF is antituberculosis drug???..Ethambutol..
73)Relience take over vch air li9ne?
74)Antinomycin D nd Rifampicin related confusin ques
76)DNA polymerase havin activity??...5 to 3,3 to 5,5 to 3 wth exonuclease,
77)SP angle…180
78)sesqueterpene havin isoprene unit,,,ans 3
79)In chewable tablet vch is usd?? Mannitol…
80Manitol used bz..Ans negativ heat f soln
81)CAP hydrolyze at pH….2.1..3.3…5.4….Ph indepedant
82)Anandamide….
83)Condensed tannin…Ans proanthocyanidin
84)Not sterilized by moist heat…taflon,polystyrene,polyethylene
85)leucopenia…decrese size of WBC,increase size f WBC
86)Estrogen higher level vch toxicity produce??...wieght loss,thrombophlebitis…
87)exothermic reaction Enrgy f product….Less,more
88)Father f pharmacognosy..hippocrates
89)benzyme intermediate..
90)Organic cmpd+UV….electronic transition
91)Quantitativ estimation by..UV,IR,Mass,Nmr
92)St phase in cellulose chromatography…silica gel,water without OH.water with OH
94)PEG liposome….
95)WOF is wrong…aquacoat means enteric coatin
96)WOF is nt disacchrides….sucrose,maltose,lactose,glucopyranose
97)Glycolysis occur in…cytosol,mitochondia,nucleolus,nucleus
WOF occur in mitochondria..steroid synthesis,fat synthesis,
98)feed back inhibitin…
99)composite family nd one source belong to….terpene,alkaloids,glycoside,tannis
100)IR activity seen…change in dipole moment…
101)300 Mhz…c13 Nmr???.....75
102)Increse polarity..n to pi* transitn…bathochromic shift,hypsochromic shift…
103)WOF increase the QT interval…terfenadine nd other 3 option
104)WOF is action of diuretic..Urine formation,glucose formation,
105)Metabolite of hormone stored in…pancreas,adrenal medulla..
106)Bile is stored in…pancreas,gall blader,
107)Body Temp controlled by…hypothalamus…
108)Iregulation in moment due to…..cerebrum,cerebellu,
109)cardiac output/min calld……..cardiac cycle,cardiac output,force f contraction
110)most intense peak…Base peak…
111)Molar extinction coefficient Unit….
112)Acute amoebic dysentery vch drud used..metronidazole,chloroquine..
113)Flourouracil..ans inhibit thymidylate synthesis…
114)Folate deficiency by…methotraxate..
115)NSAIDS induced GITproblem handled by…mesoprostol
116)Insulin ph 5..hw to make longer actin insulin lyk dt ques…increase pH,lower pH
117)Longer actin penicillin…procain penicillin and other qption
118)WOF used as sorbent in tablet??.....MCC,silica,both,none
119)Acetylene value……ans lower than alkene
120)free radical stability….
121)free radical str…..ans planar
122)str of twisted boat…..
123)Tartaric acid inactive bz…..internal plane f symmetry..
124)WOF is prodrug..sulindac,sulphasalazine,aspirin
125)WOF is induced in allergy…IgE
126)WOF is participate in complement sym…IgG,IgM,IgE,IgA
127)Disinfectant fluid….ans Sch O
128)Vasaka leaf shape…ans lanceolate
129)glandular type,,,fracture….
130)agaropectin made up f….galactose nd uronic acid,glucose nd uronic acid
131)Arhenious Eqn related ques
132)Handersn hechalbatch…pH
133)Inflamation f brain…Ans meningitis…
134)GABA..increse cl level
135)Stainin..WOF is true abt gram positive stain
136)Eculle method 4 ans volatile oil
137)Vulcanizin agent…..S,SO2
138)IND full form
139)WOf is not product f dabur….meswak,glucose D,odomus
140)Colour added in vch step….syrup coatin
141)Interfacial tensn measured by..ostwald,brook field
142)vch is adultrant f saraca indica
143)tablet strength increser by ques lyk dat…..MCC,lactose
144)Mg stearate added in vch step of wet granulation…durin granulation,aft granulation
145)GC principle…adsorption,partition,both
146)Na salt f sachrin usd as….solublizin agent,bulkin gent,aweetnin agent
147) IV emulsion isotonic wth,,Nacl,KCL
148)IP h2O2….20%,80% lyk ques
149)Arsenic test apparatus use??…nessler cylinder
150)Doctor without border smthin lyk ques
151)subsidy definition..
152)dideoxy nucleotide differ frm deoxy nucleotide by…….less OH at 3rd carbon,More OH at 3rd carbon,lessH at 3rd carbon,more H at 3rd carbon
153)In m-RNA nucleotides are joinee by…phosphodiester bonds,glycosidic bond,hydrogen bond
154)Vd=X/C related ques,,ans 5 L
155)WOF is stron base….dimethyaniline,Pyrole,aniline,Pyridine
156)Enteric coated takes time in 0.1 N hcl…60,120,180,45
157)WOF used in efervesent tablet…citric acid+Na bicarbonate.
158)Wet granulation vch is nt used…Roler compactor,sigma blade mixer.
159)Contact angle related ques
160)Draves test,,ans weting angle
161)Cafeeine gives..ans murexide test
162)Meyer’s reagent….
163)Rhem rhizome use…..purgative,carminative,
164)Meltin f DNa increase..adeneni nd guanine,adenine nd thiamine,cytosine nd thiamine,
165)Topotecan…natural,synthetic,
166)H.pyroli induced hyperacidenia treated by???
167)clonidine….Antihypertensive,
168)Daughter cells divided in…Prophase,Anaphase,telophase
169)Company acquire vch hospital???..
170)Cyanide 540 UV gives colour……Blue,green,Red
171)PCI constituted by…central govt,state govt…
172)Carbopol….PVA,PVP
173)antioxidant wth reducing Prop??...tocopherol,hydroxyurea
174)Preservative used in ophthalmic??benzal konium Cl
175)Pharmaceutical Rotation by…molecule,crystal,both,None..
176)Increase lipase level indicate vch organ functn test…
177)USP apparatus 2…ans Paddle..
178)Streptomycin side effect….ans vestibular disturbance
179)Podophylotoxin…lignan dvt….
180)str of ketone treated wth LiAlH4

estimation of multi-component formulations

2011-09-08T00:08:00.000-07:00

Spectrophotometric multi-component analysis

Absorption spectroscopy is one of the most useful and widely used tools available to the analyte for quantitative analysis. The relation between the concentration of analyte and the amount of light absorbed is the basis of most analytical applications of molecular spectroscopy. This method of analysis is gaining importance due to simple, rapid, precise, highly accurate and less time consuming. Spectrophotometric multi-component analysis can be applied where the spectra of drugs overlaps.In such cases of overlapping spectra, simultaneous equation can be framed to obtain the concentration of individual component; otherwise multi-component analysis can be applied on any degree of spectral overlap provided that two or more spectra are not similar exactly. Some examples are listed in table-2.
The various spectroscopic techniques used for multi-component analysis are as follows

Simultaneous equation method (Vierodt’s method)³

Concentration of several components present in the same mixture can be determined by solving a set of simultaneous equation even if their spectra overlap. If Beer’s law is followed, these equations are linier.

Two wavelength method³

The method can be used to calculate the concentration of component of interest found in a mixture containing it along some unwanted interfering component. The absorption different between two points on the mixture spectra is directly proportional to the concentration of the component to be determined irrespective of the interfering component.

The absorption ratio method³

The absorbance ratio method is a modification of the simultaneous equation procedure. It depends on the property that for a substance, which obeys Beer’s law at all wavelength, the ratio of absorbance at any two wavelengths is constant value independent of concentration or path length. e.g. Two dilutions of the same substance give the same absorbance ratio A₁ / A₂. In the USP, this ratio is referred to as Q value. In the quantitative assay of two components in admixture by the absorbance ratio method, absorbances are measured at two wavelengths. One being the λ _maxof one of the components (λ₂) and the other being a wavelength of equal absorptivity of the two components (λ₁), i.e., an iso-absorptive point.

Geometric correction method³

A number of the mathematical correction procedures have been developed which reduce or eliminate the background irrelevant absorption that may be present in the samples of biological origin. The simplest of this procedure is the three-point geometric procedure, which may be applied if the irrelevant absorption is linier at the three wavelengths selected. This procedure is simply algebraic calculations of what the baseline technique in infrared spectrophotometry dose graphically.

Absorption factor method (Absorption correction method)³

It is further modification of simultaneous equation method. Quantitative determination of one drug is carried out by E (1%, 1 cm) value and quantitation of another drug is carried out by subtraction absorption due to interfering drug using absorption factors.

Orthogonal polynomial method³

The technique of orthogonal polynomials is another mathematical correction procedure, which involves complex calculation than the three-point correction procedure. The basis of the method is that an absorption spectrum may be represented in terms of orthogonal functions.

Difference spectrophotometry³

Difference spectrophotometry provides a sensitive method for detecting small changes in the environment of a chromophore or it can be used to demonstrate ionization of a chromophore leading to identification and quantitation of various components in mixture. The essential feature of difference spectrophotometric assay is that the measured value is the difference absorbance (∆A) between two equimolar solutions of the analyte in different chemical forms, which exhibits different spectral characteristics.

Derivative spectrophotometry³

Derivative spectrophotometry is useful means of resolving two overlapping spectra and eliminating matrix interference due to an indistinct shoulder on side of an absorption bands. It involves conversion of normal spectrum [A= f (λ)]to its first [dA/ dλ = f (λ)], second [d²A/ dλ² = f (λ)]and higher derivatives spectra where the amplitude in the derivative spectrum is proportional to the concentration of the analyte provided that Beer’s law is obeyed by the fundamental spectrum.

Area under curve method⁴

In this method, the absorptivity values (ε₁andε₂) of each of the two drugs were determined at the selected wavelength range. Total area under curve of a mixture at wavelength range is equal to the sum of area under the individual component at that wavelength range. This method is applicable when the λ _maxof the two components are reasonably dissimilar, the two components do not interact chemically and both the component must be soluble in same solvent.
The methods deviated when overlapping of UV spectra of two drugs significantly and large difference in labeled strength⁵. e. g. Tizanidine HCl 3.0 mg and nimesulide 100.0 mg per tablet. The accuracy of the method depends upon nature of solvent, pH of solution, temperature, high electrolyte concentration and the presence of interfering substances.

High performance liquid chromatography (HPLC):

This technique is based on the same method of separation as classical column chromatography. i.e. adsorption, partition, ion exchange and gel permeation but it differ from column chromatography, in that mobile phase is pumped through the packed column under high pressure. The technique is most widely used for all the analytical separation technique due to its sensitivity, its ready adaptability to accumulate quantitative determinations, its suitability for separating nonvolatile species or thermally fragile ones. In normal HPLC, polar solids such as silica gel; alumina (Al₂O₃) or porous glass beads and non-polar mobile phase such as heptane, octane or chloroform are used but if the opposite case holds, it is called as reversed phase HPLC. Some examples are listed in table-3 and 4

High performance thin layer chromatography (HPTLC):

The principle is based on plane chromatography. The mobile phase normally is driven by capillary action. The prominent advantages of this technique includes possibilities of separating of up to 70 samples and standard simultaneously on a single plate leading to high throughout, low cost analogs and the ability to construct calibration curves from standard chromatography under the same condition as the sample. Analyzing a sample by use of multiple separation steps and static post chromatographic detection procedures with various universal and specific visualization regents that are possible because all the sample components are stored on the layer without the chance of loss. Some examples are listed in table-5.

Gas chromatography (GC):

GC is one of the most extensively used separation technique in which separation is accomplished by partitioning solute between a mobile gas phase and stationary phase, either liquid or solid. The chief requirement is same degrees of stability at the temperature necessary to maintain the substance in gas state. Some examples are listed in table-6.

Validation of methods⁶:

Validation by definition is an act of providing that any process, method, equipment, material, activity, system or analyst performs as expected under given set of conditions. When extended to an analytical procedure, depending upon the application it means that a method works reproducibility when carried out by a same or different person, in same or different laboratories, using different regent, different equipment etc. It will ensure commitment to quality of products and services. It builds a degree of confidence not only for the developer but also to the user.
Validation of analytical method should follow a well documented procedure beginning with the definition of the scope of the method and its validation criteria and including the compounds and matrices, desired detection and quantitation limits and any other important performance criteria. The scope of method should include different equipment and locations where the method will be run. The methods were validated in terms of linearity, accuracy, precision, specificity and reproducibility of sample applications. Analytical method validation has been performed according to ICH guidelines. Accuracy of the method is certain on the basis of recovery studies performed by the standard addition method. The formula used for calculating recovery of pure drug is
Percentage recovery = T - A X 100 / S
Where T = Total amount of drug estimated
A= Amount contributed by formulation
S = Amount of pure drug added.
Precision of analytical method is expressed as SD and RSD of series of measurement by replicate estimation of drug.
The stability indicating ability of the method has been investigated by deliberately degrading the sample preparation. The stress conditions applied are acidic (0.1 M HCl), alkalis (0.1M NaOH) and mild oxidizing condition (3% H₂O₂) for 24 hr at 50 C. Also heat (60C) and U.V. exposure for 24 hr will be carried out on the sample.
The linearity of the method was investigated by serially diluting the stock solutions of drugs and measured values.
Ruggedness studies has been carried out for different parameters i.e. days and analysts. The results shall be compared with the method.

Biopharmaceutical Classification Of Drugs

2011-09-07T22:03:00.000-07:00

Biopharmaceutical Classification System:

The biopharmaceutical classification system was developed primarily in the context of immediate release (IR) solid oral dosage forms. It is the scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability (2). It is a drug development tool that allows estimation of the contributions of three major factors, dissolution, solubility and intestinal permeability that affect oral drug absorption from immediate release solid oral dosage forms. The interest in this classification system is largely because of its application in early drug development and then in the management of product change through its life cycle. It was first introduced into regulatory decision-making process in the guidance document on Immediate Release Solid Oral Dosage Forms: Scale Up And Post Approval Changes (3).

Classification:

According to BCS, drug substances are classified as (Figure 3):

Class I : High Solubility – High Permeability

Class II : Low Solubility – High Permeability

Class III: High Solubility – Low Permeability

Class IV: Low Solubility – Low Permeability

Combined with the dissolution, the BCS takes into account the three major factors governing bioavailability viz. dissolution, solubility and permeability.

This classification is associated with drug dissolution and absorption model, which identifies the key parameters controlling drug absorption as a set of dimensionless numbers viz.

Absorption number, defined as the ratio of the mean residence time to mean absorption time.
Dissolution number, defined as the ratio of mean residence time to mean dissolution time.
Dose number, defined as the mass divided by the product of uptake volume (250 ml) and solubility of drug (4).

Class I drugs exhibit a high absorption number and a high dissolution number. The rate limiting step is drug dissolution and if dissolution is very rapid then gastric emptying rate becomes the rate determining step. e.g. Metoprolol, Diltiazem, Verapamil, Propranolol.

Class II drugs have a high absorption number but a low dissolution number. In vivo drug dissolution is then a rate limiting step for absorption except at a very high dose number. The absorption for class II drugs is usually slower than class II and occurs over a longer period of time. In vitro- In vivo correlation (IVIVC) is usually excepted for class I and class II drugs. e.g. Phenytoin, Danazol, Ketoconazole, Mefenamic acid, Nifedinpine.

For Class III drugs, permeability is rate limiting step for drug absorption. These drugs exhibit a high variation in the rate and extent of drug absorption. Since the dissolution is rapid, the variation is attributable to alteration of physiology and membrane permeability rather than the dosage form factors. e.g. Cimetidine, Acyclovir, Neomycin B, Captopril.

Class IV drugs exhibit a lot of problems for effective oral administration. Fortunately, extreme examples of class IV compounds are the exception rather than the rule and are rarely developed and reach the market. Nevertheless a number of class IV drugs do exist. e.g. Taxol.

Applications of BCS in oral drug delivery technology (5):

Once the solubility and permeability characteristics of the drug are known it becomes an easy task for the research scientist to decide upon which drug delivery technology to follow or develop.

The major challenge in development of drug delivery system for class I drugs is to achieve a target release profile associated with a particular pharmcokinetic and/or pharmacodynamic profile. Formulation approaches include both control of release rate and certain physicochemical properties of drugs like pH-solubility profile of drug.

The systems that are developed for class II drugs are based on micronisation, lyophilization, addition of surfactants, formulation as emulsions and microemulsions systems, use of complexing agents like cyclodextrins.

Class III drugs require the technologies that address to fundamental limitations of absolute or regional permeability. Peptides and proteins constitute the part of class III and the technologies handling such materials are on rise now days.

Class IV drugs present a major challenge for development of drug delivery system and the route of choice for administering such drugs is parenteral with the formulation containing solubility enhancers.

Conclusion:

The in vivo performance of the drug depends upon its solubility and permeability. The biopharmaceutical classification system is the guiding tool for the prediction of in vivo performance of the drug substance and development of drug delivery system to suit that performance. The knowledge of the biopharmaceutical class of the drug substance is also essential for biowaivers thereby reducing the cost both in terms of money and time.

References:

1. Draft Guidance for Industry, Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms containing certain Active Moieties/ Active Ingredients based on a Biopharmaceutic Classification System, February 1999, CDER/FDA.

2. Amidon G.L., Lennernas H., Shah V.P., Crison J.R.A., A Theoretical Basis For a Biopharmaceutic Drug Classification: The Correlation of In Vitro Drug Product Dissolution and In Vivo Bioavailability. Pharm. Res. 12: 413-420 (1995).

3. Guidance for Industry, Immediate Release Solid Oral Dosage Forms: Scale Up and Post Approval Changes, November 1995, CDER/FDA.

4. Medicamento Generico from website http://www.anvisa.go/.

5. Devane J., Oral drug delivery technology: addressing the solubility/ permeability paradigm, Pharm. Technol. 68-74, November 1998.

USP Minimum Sample Weight

2011-08-11T03:32:00.000-07:00

Minimum sample weight is defined as the minimum sample quantity required by a balance or scale to obtain a reliable result, taking into account factors such as measurement uncertainty. In the pharmaceutical industry, the United States Pharmacopoeia (USP) is widely recognized as the official authority that prescribes the requirements for determining minimum sample weight.

According to USP Chapter <41> Weights and Balances ⁱ, measurement uncertainty should satisfy the following requirements:

The measurement uncertainty of a balance or scale does not exceed 0.1% of the reading.
Three times the standard deviation ⁱⁱ, as determined by at least 10 replicate weighings, does not exceed 0.001 (0.1%) when divided by the amount weighed.

The conditions above can be expressed using the following equations:

Resolution	Model	Capacity	Repeatability (σ)	Measurement Uncertainty (3σ)	Minimum Sample Weight
0.01mg	GH-202	51g (Fine range)	0.02mg	0.06mg	60mg
0.01mg	GR-202	42g (Fine range)	0.02mg	0.06mg	60mg
0.1mg	GH-200	220g	0.1mg	0.3mg	300mg
0.1mg	GR-200	210g	0.1mg	0.3mg	300mg
0.001g	GX-200	210g	0.001g	0.003g	3g
0.01g	GX-2000	2100g	0.01g	0.03g	30g

Comparison of Matrix Effects in HPLC-MS/MS

2011-08-04T02:03:00.000-07:00

Jet C. Van De Steene and Willy E. Lambert

Laboratory of Toxicology, Ghent University, Ghent, Belgium

When developing an LC-MS/MS-method matrix effects are a major issue. The effect of

co-eluting compounds arising from the matrix can result in signal enhancement or suppression.

During method development much attention should be paid to diminishing matrix

effects as much as possible. The present work evaluates matrix effects from aqueous

environmental samples in the simultaneous analysis of a group of 9 specific pharmaceuticals

with HPLC-ESI/MS/MS and UPLC-ESI/MS/MS: flubendazole, propiconazole, pipamperone,

cinnarizine, ketoconazole, miconazole, rabeprazole, itraconazole and domperidone. When

HPLC-MS/MS is used, matrix effects are substantial and can not be compensated for with

analogue internal standards. For different surface water samples different matrix effects are

found. For accurate quantification the standard addition approach is necessary. Due to the

better resolution and more narrow peaks in UPLC, analytes will co-elute less with interferences

during ionisation, so matrix effects could be lower, or even eliminated. If matrix effects

are eliminated with this technique, the standard addition method for quantification can be

omitted and the overall method will be simplified. Results show that matrix effects are almost

eliminated if internal standards (structural analogues) are used. Instead of the time-consuming

and labour-intensive standard addition method, with UPLC the internal standardization can

be used for quantification and the overall method is substantially simplified. (J Am Soc Mass

NIPER question paper 2009

2011-01-26T13:45:00.001-08:00

NIPER Question
1. Which is cytotoxic from following marine? (bryostatin)
2. To avoid crystallization of syrup which substance is added? (polyhydric alcohols)
3. Particle size of fluid energy mill is? (1-30micrometer)
4. Use of Gallic acid? (Antioxidant)
5. HLB of o/w emulsion. (3-8)
6. Range of Visible light? (400-800nm options were in micro so read questions carefully
before attaining )
7. Source of IR (Nerst glower)
8. Hydrogen bonding determined by which method? (Raman)
9. Most intense peak in MASS spectra? (Base peak)
10. How to determine non-UV active structure? (derivatization)
11. Energy comparison of UV, IR n NMR. Means put them in ascending order of their energies.
(NMR least<ir
12. Reference standard used in NMR? (TMS)
13. In IR calibration which substance is used? (Air)
14. What does RS means in IP? (Reference standard)
15. Sparingly soluble? (30 to 100 parts)
16. Cough is S/E of? (captopril)
17. Capsule '000' size capacity?
18. Green bones are made up of which type of gelatin? (type B)
19. Vehicle used in SGC?
20. Which property not related to polymorphism? (chemical assay)
21. Ostwald ripening is related with? (suspension)
22. Osmotic pressure of blood is?
23. Duration of nasal delivery
24. Duration of mucoadhesive delivery
25. Largest cotton producing country
26. Free trade port in India? (Kandla)
27. Amoebiasis is caused by? (E.histolytica)
28. In clock 12'o clock is north east then at 1:30pm what would be direction? (East)
29. In monosubstituted cyclohexane which structure will be stable?
30. Stereochemistry of Alanine
31. Linkage in amylase
32. Teratogenic vitamin? (A)
33. In cyclic carbohydrates stereochemistry is known as? (anomer)
34. Propranolol is contraindicated in? (Asthma)
35. Highest first pass metabolism of following?
a. propranolol (ans) b. digoxin c. Phenobarbital d. phenytoin
36. Which of this is cardiotoxic (Adriamycin)
37. M/A of paclitaxol is?
38. Therapeutic index denotes (Margin of safety)
39. Selective ï ¡ 1 blocker is? (Prazosin)
40. Activity of receptor (drug selectivity and selective antagonist action of drug)
41. Receptors are made up of? (protein)
42. Cytokinins are?
43. Morphine act through ï receptor.
44. Nicotinic receptor work through which messenger system?
45. Example of Neurodegenerative disorder. (Alzheimer's Disease)
46. Action of Ach? (Hastens G.I. emptying)
47. Name of Indian Ginseng? (Withania Somnifera)
48. Father of Chemotherapy? (Paul Ehrlich)
49. Out of following which is not containing bacteria?
a. Soil b. Ice c. Dust d. Blood (ans) (blood is sterile unless infected)
50. Drug approved by US FDA for alopecia? (Minoxidil)
51. Drug interaction is hazardous of following? (terfinadin + erythromycin)
52. Which of following cause cardiac arrhythmia? (terfinadin)
53. ï ¢2 selective(salbutamol)
54. Cerebral Malaria (quinine)
55. Which malaria is deadly? (P. falciperum)
56. Use of Primaquine is? (choloroquine resistant P. falciperum)
57. Tamoxifen used in breast cancer act as? (estrogen antagonist)
58. Metallic elements detected by? (AAS)
59. Enthalpy is measure of?
60. Luminescence, fluorescence and phosphorescence is a type of? (Emission spectroscopy)
61. Rate Kinetic deals with? (order, molecularity and conc of reactant)
62. In exothermic process increase in temp indicate what?
a. Reactant is more b. product yield is more(ans) c. Rxn stopped d. equilibrium
63. Cough syrup mostly contains which alkaloid? (Codeine)
64. Terpenoid are obtained from which biosynthetic pathway?
65. In diosgenin which ring is present?
66. In triterpenoid how many isoprene units are present? (6)
67. In dipeptide bond how many amino acids are present? (3)
68. Which of following contain chromosome or DNA?
a. mitochondria (ans) b. ER c. Golgibody d. cytoplasm
69. t-RNA function
70. Inhibition of mammalian gene expression is at the level of?
71. IPEC deals with?
a. Excepient (ans) b. US FDA c. GMP d. GLP (International Pharmaceutical Excipient Council)
72. ABC analysis deals with? (Inventory control)
73. Phase- IV deals with?
74. IND is for? (filling of NCE New Chemical Entity now changed to NME New Molecule Entity as biomolecules are not considered as chemical)
75. Minimum velocity required for laminar air flow unit? (100)
76. Cardiac Ca++ channel blocker? (nifedipine)
77. Ca++ channel use which type of messenger system?
78. Fill in the gap: stu_ _ st _ _ ws _ _ vw (vwuvtu)
79. Which of following is endothermic?
a. Adsorption b. crystallization c. vaporization d. all
80. Betaine structure (Refer Wittig reaction)
81. Structure of nifedipine.
82. Stereochemistry in biphenyl
83. How to determine unsaturation? (bromination,hydrogenation,ozonolysis)
84. NMR signal obtained in 1,4- dioxane (1 peak)
85. Reaction occurring in ethane? (E1 )
86. Tomato red pigment is due to? (Lycopene)
87. Insulin act on which cells? (Beta)
88. PG released by (COX-II)
89. Aspirin is? (Irreversible COX inhibitor)
90. Phenytoin used in? Digitalis induced arrhythmia)
91. Serotonin is neurotransmitter
92. Alcohol dehydrogenase converts (ethanol to acetaldehyde)
93. Major product obtained from purine metabolism is? (Uric acid)
94. Saffron cultivated in (Jammu n Kashmir)
95. Benzyl alcohol 1% is used as Preservative
96. Cetyl ether of Polyethylene glycon is known as? (Cetomacrogol)
97. Detector used in spectrophotometer? (Photo multiplier tube)
98. Living organisms are detected by? (Dark field microscopy)
99. Which of following is not static? (Flash dryer)
100. Rifampicin used not only in TB but also in? (Leprosy)
---------------------------
01. Immunoglobulin is? (2 light, 2 heavy, disulfide)
02. Which of following not causing enzyme induction? (Sulfonamide)
03. Detector used in IR? (Thermocouple)
04. Function of microvilli is? (Increase surface area)
05. pH of 0.005M HCL?
06. pH of pKa 5.4 is?
07. IR range of CO (acid chloride)
08. Neostigmin does not cross BBB? (Polar)
09. Drugs which cross BBB are? (lipophilic drugs)
10. Which is most commonly used HPLC? (Reverse Phase)
11. Phenolphthalein is? (Acid base indicator)
12. Drug assayed by acid-base back titration? (Aspirin)
13. Which of following is titrated using strong base? (Refer IP for titrations, this can be
considered as important)
14. Amiloride and Spiranolactone differs in?
15. Statin mechanism? (Reduce cholesterol)
16. Which of following is not related with enalapril (It is not an AT1 antagonist)
17. Equation of Angle of Repose.
18. Character of liposome is?
19. Eye drops and parentral differ in?
20. Colchicines is used in Gout.
21. Omeprazole act by?
22. Muscarinic antagonist used in ulcer.
23. Most commonly used in PD? (L-dopa)
24. Dopamine agonist used in PD. (Bromocryptine)
25. Which of this is not acting on nuclear receptor? (Amino acid trypsin)
26. Nucleus present in coumarin.
27. Which of following is used in vascular disorder? (Ginko biloba)
28. Podophyllotoxin is? (Lignan)
29. Bacterial cell wall consists of? (Heteropolysaccharide)
30. In indole biosynthesis which AA is used? (Typtophan)
31. Sugar in protein preparation act as? (cryoprotective)
32. Non aq. Binder
33. Flow of genetic information (DNA to RNA to Protein)
34. Iodine Value
35. SDS-PAGE is used for? (Protein)
36. Yield calculation of synthesis.
37. Thermal assay (DSC)
38. Auxochrome function.
39. Supreme commander? (President)
40. Vant Hoff equation
41. Nitrites? (Vasodilation)
42. CH3 F (deshielded so downfield)
43. Expiry date determined by use of drug along with container.
44. Which is most permeable to moisture? (Polyethylene)
45. Accelerated stability study is done at what temp n RH?
46. Dose required for intradermal delivery.
47. Aim of welfare state.
48. Solubilsation is based on (Stereochemistry)
49. Circular diachronism spectroscopy is used for? (Optically active compound)
50. Simple and compound interest calculation.
51. Digitalis acts by Na+ / K+ ATPase Pump
52. Syphilis is caused by?
53. Acetazolamide? (Carbonic anhydrase inhibitor)
54. Unit of delta(ppm)
56. HIV is caused by? (Virus)
Apart from this is contains many mathematical calculations, synonyms, antonyms and acronyms.

(And same paper is their for MBA and MS)

Note: In form they provide one option for sponsor seat do tick that option it do not require any industrial recommendation but it is one sort of payment seat. If you don't tick that option you will not be eligible for taking admission in payment seat.

Few useful acronyms.
1. CPCSEA- Committee for Purpose of Control and Supervision of Experimental Animals.
2. IAEC- Institutional Animal Ethics Committee
3. BEA-Breeding for Experimental Animals
4. SDS-PAGESodium Dodecyl Sulfate- Polyacrylamide Gel Electrophoresis
5. NME- New Molecular Entity
6. NCE- New Chemical Entity
7. GRAS- Generally Accepted As Safe
8. ANDA- Abbrevated New Drug Application (Generic filling)
9. IIG- Inactive Ingredient Guide

Note: Answers given in bracket is best of the options given. It might not be the most appropriate answer for that question. And don't rely on answer completely we have wrote what we were able to remember so please do check textbooks.

NIPER JEE 2005

flow injection system in HPLC?
fingerpoint region in IR?
trance stilbens?
alfa and beta d-glucose structure?
most suitable diluent for controlled releae/
solvents in reverse phase chromatography?
RNA and DNA str?
reverse transcriptase enzyme?
chloroquin used in ..?
artemisin ?
asparginase?
kaalfischer titration?
alkaloid which is not therapeutical active?
configuration of ephedrine/
endogenous anticoagulant?
Sulfonylureas?
what happend in type 2 daibetes?
afficacy and affinity?
What is nitric oxide?
type of Ca++ present in heart?
Action of dopimine?
antagonist of levodopa?
First law of thermodinamicss/
cubic nature of NACl?
mechanism of adaptogen/
NMR
UV calculation
mass calculation of fragments?
rimer-timen reaction.
Find distereomers?
route of administration?
gingival hyperplasia is a side effect of?
isoprene unit of FPP?
analytical technique of noble druges?
stop codon?</ir

effect of cancer chemotherapy on reproduction and sexuality

2011-01-12T00:31:00.000-08:00

Reproduction and sexuality

Reproductive and sexual problems can occur after you receive chemotherapy. Which, if any, problems develop depends on your age when you are treated, the dose and duration of the chemotherapy, and which chemotherapy drugs are given.

Sexual changes men may experience

Most men on chemotherapy still have normal erections. A few, however, may develop problems. Erections and sexual desire often decrease just after a course of chemotherapy, but usually recover in a week or two. A few chemotherapy drugs, for example cisplatin or vincristine, can permanently damage parts of the nervous system. Although it is not yet proven, these drugs may interfere with the nerves that control erection.
Chemotherapy can sometimes affect sexual desire and erections by decreasing the amount of testosterone produced. Some of the drugs used to prevent nausea during chemotherapy can also upset a man's hormone balance, but hormone levels should return to normal after treatments have ended.
Many chemotherapy drugs can affect sperm and the parts of the body that produce them. Some of these effects may be permanent. Freezing sperm before chemotherapy begins is one option for men who wish to father children later in life. (If you would like to read more about this, see our document called Fertility and Cancer: What Are My Options?)
Although it is sometimes possible to father children during chemotherapy, the toxicity of some drugs may cause birth defects. Because of this, it is suggested that all men getting chemotherapy take precautions and use a reliable type of birth control if they are sexually active.
Chemotherapy may suppress your immune system. If you have had genital herpes or genital wart infections in the past, you may have flare-ups during chemotherapy.
Chemotherapy is often given through an IV tube into the bloodstream. However, new ways have been developed to get drugs directly to a tumor. For cancer of the bladder, for example, chemotherapy is placed right into the bladder through a catheter in the urethra. Such a treatment has only a minor effect on a man's sex life. You may notice some pain if you have sex too soon after the treatment. This is because the bladder and urethra are still irritated.
For more information, please see our document Sexuality for the Man With Cancer.

Sexual changes women may experience

Many chemotherapy drugs can either temporarily or permanently damage a woman's ovaries, reducing their output of hormones. This affects a woman's fertility and libido (sex drive). Ovarian function is less likely to return in women over age 30, so they are more likely to go into menopause. (If you would like to read more about preserving fertility, see our document called Fertility and Cancer: What Are My Options?) Symptoms of early menopause include hot flashes, vaginal dryness and tightness during intercourse, and irregular or no menstrual periods. As the lining of the vagina thins, light spotting of blood after intercourse becomes common.
Even though menstrual cycles may be disrupted or stopped with chemotherapy, it may still be possible to get pregnant at this time. The toxicity of some chemotherapy drugs may cause birth defects. Because of this, women getting chemotherapy should take precautions and use a reliable type of birth control if they are sexually active.
Some chemotherapy drugs irritate all mucous membranes in the body. This includes the lining of the vagina, which often becomes dry and inflamed (a condition called vaginitis).
Vaginal infections are common during chemotherapy, particularly in women taking steroids or powerful antibiotics used to prevent bacterial infections. Yeast cells are a natural part of the vagina's cleansing system. If too many grow, however, you may notice itching inside your vagina, a whitish discharge that often looks like cottage cheese, or a burning sensation during intercourse. Yeast infections can sometimes be prevented by not wearing pantyhose, nylon panties, or tight pants. Loose clothing and cotton panties allow better air circulation. Your doctor may also recommend a vaginal cream or suppository to reduce yeast cells or other organisms that grow in the vagina. Most of these medicines can be bought without a prescription, although there are treatments that can be taken by mouth that must be prescribed by a doctor. It is very important to have vaginal infections treated if you are getting chemotherapy. Your body's immune system is not as strong because of the treatment, and any infection may become a more serious problem if it is not dealt with as early as possible.
If you have had genital herpes or genital wart infections in the past, you may have flare-ups during chemotherapy. This is because the chemotherapy suppresses your immune system.
Chemotherapy is often given through an IV tube into the bloodstream. However, new ways have been developed to bring drugs directly to a tumor. For cancer of the bladder, for example, chemotherapy is placed right into the bladder through a catheter in the urethra. Such a treatment usually has only a minor effect on a woman's sex life. You may notice some pain if you have sex too soon after the treatment. This is because the bladder and urethra are still irritated

Over-the-counter drug

2010-12-09T12:31:00.000-08:00

Over-the-counter (OTC) drugs are medicines that may be sold without a prescription, in contrast to prescription drugs. The name "over-the-counter" is somewhat confusing to some, since these items can be found on the shelves of stores and bought like any other packaged product in some countries or in others may be bought "over the counter" from the pharmacy, while prescription drugs are sold at a pharmacy counter. The term likely dates back to before self service shopping became common, when most goods were obtained by requesting them from a clerk at a sales counter; while prescription drugs required a visit to the doctor first, these drugs could be purchased "over the (sales) counter" just like other goods. Some medicines considered safe in general terms may be available in general stores, supermarkets, gas stations etc. The rules vary considerably from country to country. Regulation by country United States U.S. drug regulation In the United States, the manufacture and sale of OTC substances is regulated by the FDA. The Federal Food, Drug, and Cosmetic Act requires that all "new drugs" are required to obtain a New Drug Application ("NDA") prior to entering interstate commerce, but the act exempts any drugs generally recognized as safe and effective ("GRAS/E") from this requirement. In order to fit the vast amount of OTC drugs that were already on the market prior to the requirement that all drugs obtain an NDA, the FDA created the OTC monograph system to review classes of drugs and categorize them as GRAS/E by regulation. This meant that certain classes of OTC drugs were not required to obtain an NDA and could remain on the market. Thus, manufacture must be done either pursuant to an FDA monograph, which specifies types of OTC drugs, active ingredients and labeling requirements, or pursuant to a New Drug Application (NDA), for products which do not fit within a specific monograph. Because an NDA is extremely expensive to obtain, due primarily to testing requirements, most OTC substances produced in the USA are sunscreens, anti-microbial and anti-fungal products, external and internal analgesics such as lidocaine and aspirin, psoriasis and eczema topical treatments, anti-dandruff shampoos containing coal tar, and other topical products with a therapeutic effect. The Federal Trade Commission regulates advertising of OTC products. This is in contrast to prescription drug advertising, which is regulated by the FDA. United Kingdom In the United Kingdom, medication will fall into one of three categories: Prescription Only Medication, which is only available with a valid prescription from a doctor. A pharmacist has to be on the premises for POM medicines to be dispensed, required by law. The medicine has been specifically prescribed for the patient holding the prescription, so it is considered safe for only the recipient to take. [POM] Pharmacy Only Medication, containing chemicals, strengths or sizes which require more information, personal to the person taking the medication. The pharmacist will determine whether the medicine is safe for the particular customer based on their responses to a set of questions. [P] General Sale License, available off the shelf with no pharmacy training required to sell. Generally considered safe for most people when taken correctly. [GSL] Medication available only with a prescription is marked somewhere on the box/container with [POM]. Over-the-counter medicines are marked with [P]. A prescription is not required for [P] medicines and pharmacy sales assistants are required by law to ask certain questions, most of all, whether the patient is taking other medication, before selling these. It is with this information that the pharmacist can halt the sale, if need be. Some medication available in supermarkets and petrol stations is sold there only in smaller packet sizes. Often, larger packs will be marked as [P] and available only from a pharmacy. Frequently, customers buying larger than usual doses of [P] medicines (such as Paracetamol) will be queried, due to the possibility of abuse. Non-drug OTC products In the US, medical devices may also be considered OTC. For example, most diabetic management supplies are available OTC. The category of medical devices includes electronic blood glucose monitors, monitor test strips, and lancets. In some areas insulin syringes may also be available OTC; some areas have classified all syringes as limited OTC products as a measure of drug addiction harm reduction. Switches between prescription and OTC As a general rule, over-the-counter drugs have to be primarily used to treat a condition that does not require the direct supervision of a doctor and must be proven to be reasonably safe and well-tolerated. OTC drugs are usually also required to have little or no abuse potential, although in some areas drugs such as codeine are available OTC (usually in strictly limited formulations or requiring paperwork or identification to be submitted during purchase). One of the oldest OTC drugs is aspirin. Over time, drugs that prove themselves safe and appropriate for self-medication, may be switched from prescription to OTC. An example of this is diphenhydramine (Benadryl) which once required a prescription but now is available OTC nearly everywhere. Diphenhydramine is a deliriant, nevertheless, most recreational drug users find its effects uncomfortable rather than exciting. More recent examples are cimetidine and loratadine in the United States, and ibuprofen (Herron Blue/Nurofen) in Australia. It is somewhat unusual for an OTC drug to be withdrawn from the market as a result of safety concerns, rather than market forces, though it does happen occasionally, phenylpropanolamine being one example. Recently many U.S. drugstores have begun moving products containing pseudoephedrine into locations where customers must ask a pharmacist for them. A prescription is not required; the change is allegedly being made in an effort to reduce methamphetamine production. Since the passage of the Methamphetamine Precursor Control Act, the purchase of pseudoephedrine in the United States is restricted and the identity of the purchaser is required to be obtained and recorded. In addition, pseudoephedrine itself is a mild stimulant- somewhere between caffeine and ephedrine. Nonetheless, these products are still considered OTC since no prescription is required.

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ADVANTAGES AND DISADVANTAGES OF HPLC

2010-12-09T12:23:00.000-08:00

polymeric nanoparticles as drug carrier

2010-12-09T12:18:00.000-08:00

polymeric nano particle

Md.imran ansari

1. Introduction

Ø The word nanoparticle was comes from the Greek word ‘nano’ (symbol=n).The s.i. unit is ‘nm’ (1nm=10-9).

Ø The nanoparticles are solid, colloidal particles ranging 10-1000nm in size.

Ø Tt consists of macromolecular materials in which the active ingrediants (drug or biologically active material) is dissolved, entrapped or absorbed or attached.

Ø The nanoparticles are subnanosized colloidal structure composed of synthetic or semisynthetic polymers.

Ø The polymeric nanoparticles can carry drug or proteinaceous substances that is antigen.these bioactives are entrapped in the polymer matrix as particulate enmesh or solid solution or may be bound to the particle surface by physical adsprption or chemically.

1.1.Historical Prospectives

Ø Nanoparticles are generally considered an invention of modern science; they actually have a very long history. Nanoparticles were used by Artisans as far back as the 9th century in Mesopotamia for generating a glittering effect on the surface of pots. . These nanoparticles were created by the artisans by adding copper and silver salts and oxides together with vinegar, ochre and clay, on the surface of previously-glazed pottery.

Ø

Depending on the process used for their preparation, two types of nanoparticles can be obtained.

. A.Nanospheres B.Nanocapsules

Ø Nanospheres have a matrix type structure in which a drug is dispersed, where as nanocapsules exhibits a membrane wall structure with an oily core containing the drug.

Ø As nanoparticulate system have a very high surface area, drug may also be absorbed on their surface.

Ø Nanoparticles are made of artificial or natural polymers; the use of these polymers is often restricted by their bioacceptability.

2. Types of nanoparticles

Ø Nanosized Particles

Ø Polymeric Nanoparticle

Ø Solid-Lipid Nanoparticle

Ø Nanpcrystal

Ø Nanolipid Carriers

Ø Nanoconstruct

Ø Nanoplexes

Ø Nano Coposite

Ø Nano Enclusion Compound

Ø Metallic Nanoparticle

Ø Nano Emulsion and Nano Suspension

Ø Flurescent Nanoparticle

Ø Nanochelates

Ø Nano Eggs

Ø Nano Agglomerates

3. Factors Affecting the Clearance and Biodistribution of Polymeric nanoparticles

The main factors are-

Tissue defects

Stealth properties

Targeting and the Size of the nanoparticles are major factors affecting the biodistribution and Clearance of Polymeric nanoparticles

Effect of core

Effect of surface functionality and charge

Effect of active targeting

Nanoparticle (NP) drug delivery systems (5−250 nm) have the potential to improve current disease therapies because of their ability to overcome multiple biological barriers and releasing a therapeutic load in the optimal dosage range. Rapid clearance of circulating nanoparticles during systemic delivery is a critical issue for these systems and has made it necessary to understand the factors affecting particle biodistribution and blood circulation half-life.

In this review, we discuss the factors which can influence nanoparticle blood residence time and organ specific accumulation. These factors include interactions with biological barriers and tunable nanoparticle parameters, such as composition, size, core properties, surface modifications (pegylation and surface charge), and finally, targeting ligand functionalization. All these factors have been shown to substantially affect the biodistribution and blood circulation half-life of circulating nanoparticles by reducing the level of nonspecific uptake, delaying opsonization, and increasing the extent of tissue specific accumulation.

Nanoparticles have drawn increasing interest from every branch of medicine for their ability to deliver drugs in the optimum dosage range, often resulting in increased therapeutic efficacy of the drug, weakened side effects and improved patient compliance.

Blood circulation residence, maximal tolerated dose (MTD), and selectivity are the most important factors for achieving a high therapeutical index and corresponding clinical success. Polymeric nanoparticles are defined by their morphology and polymer composition in the core and corona. The therapeutic load is typically conjugated to the surface of the nanoparticle, or encapsulated and protected inside the core. The delivery systems can be designed to provide either controlled release or a triggered release of the therapeutic molecule. The nanoparticle surface can then be functionalized by various methods to form the corona. Surface functionalization can be utilized to increase residence time in the blood, reduce nonspecific distribution, and, in some cases, target tissues or specific cell surface antigens with a targeting ligand (peptide, aptamer, antibody/antibody fragment, small molecule).

For instance, it is well established that hydrophilic polymers, most notably poly (ethylene glycol) (PEG), can be grafted, conjugated, or absorbed to the surface of nanoparticles to form the corona, which provides steric stabilization and confers “stealth” properties such as prevention of protein absorption.

Surface functionalization can address the major limiting factor for long-circulating nanoparticle systems, which is protein absorption. Proteins adsorbed on the surface of the nanoparticle promote opsonization, leading to aggregation and rapid clearance from the bloodstream. The resultant rapid clearance is due to phagocytosis by the mononuclear phagocyte system (MPS) in the liver and splenic filtration. Typically, the majority of opsonized particles are cleared by a receptor-mediated mechanism in fewer than a few minutes due to the high concentration of phagocytic cells in the liver and spleen, or they are excreted. Thus, over the past 20 years, numerous approaches to improving nanoparticle blood residence and accumulation in specific tissues for the treatment of disease have been developed.

Overcoming Biological Barriers: Effect of Physiological Defects:-

Numerous biological barriers exist to protect the human body from invasion by foreign particles. These barriers include cellular and humoral arms of the immune system as well as mucosal barriers among others. These barriers must be overcome in order for nanoparticles to reach their target (Figure 2). Due to their unique size, and amenability to surface functionalization to incorporate the desired characteristics, nanoparticles are particularly well suited to overcoming these barriers. This is especially true in the case of abnormal neovascularization. Blood vessels are responsible for delivering molecules, nutrients, and oxygen to organs throughout the body. Endothelia composing the blood vessels have been classified as continuous, fenestrated, or discontinuous, depending on the morphological features of the endothelium. The continuous endothelium morphology appears in arteries, vessels, and the lungs In contrast, fenestrated endothelium appears in glands, digestive mucosa, and kidney. Discontinuous endothelium is a characteristic of the liver (fenestrea of 50−100 nm) and bone marrow. Endothelial cells from the blood vessels are able to respond to the physiological environment, resulting in angiogenic activity. Angiogenesis is well-characterized for cancers as well as ocular and inflammatory diseases, with antiangiogenesis compounds commonly used for therapy. Angiogenesis during tumor growth results in defective hypervasculature and a deficient lymphatic drainage system, which has given rise to the concept of passive targeting of nanoparticles to tumors through the “enhanced permeability and retention” (EPR) effect. The EPR is a unique feature which allows macromolecules or drug delivery nanoparticles (cutoff size of >400 nm) to preferentially accumulate and diffuse in tumor tissues. Long-circulating drug delivery nanoparticles are able to extravasate into tumor tissues, accumulate, and release the therapeutic drug locally in the extracellular area. Similarly, abnormal neovascularization or angiogenesis as well as enhanced vascular permeability are major causes of many ocular disorders, including age-related macular degeneration (AMD), retinopathy of prematurity (ROP), ischemic retinal vein occlusions, and diabetic retinopathy (DR), causing irreversible vision loss. In ocular disorders, the angiogenic process appears to be due to a stimulus response for retinal neovascularization. The stimulus can be tissue hypoxia, inflammatory cell infiltration, increased local concentration of cytokines (VEGF, PDGF, FGF₅ TNF, IGF etc.). The result is the formation of new vessels, which disrupt the organizational structure of the neural retina or break through the inner limiting membranes into the vitreous Many other disorders are also characterized by angiogenesis or vasculature defects such as obesity asthma diabetes, and multiple sclerosis The development of new imaging systems and medical knowledge about physiological defects is leading to novel therapeutic approaches using nanoparticle drug delivery systems. It is now well accepted that nanoparticles are suitable for crossing biological barriers through tissue diffusion, extravasation, and escape from hepatic filtration.

3.1. Effect of Size

On the basis of physiological parameters such as hepatic filtration, tissue extravasation, tissue diffusion, and kidney excretion, it is clear that, along with surface composition, particle size is a key factor in the biodistribution of long-circulating nanoparticles and achieving therapeutic efficacy (Figure 2). In one study, in vivo biodistribution results of polystyrene nanoparticles with consistent composition and varying particle sizes of 50 and 500 nm showed higher levels of agglomeration of the larger nanoparticles in the liver. It was suggested that the mechanism of hepatic uptake was mediated by surface absorption of proteins leading to opsonization. However, the effect of temperature (37 °C vs 4 °C) on hepatic elimination showed unexpectedly faster uptake of the 50 nm polystyrene nanoparticles at the lower temperature. Similarly, the size of the nanoparticle was shown to have a substantial effect on the protein absorption. Small (<100 nm), medium (100−200 nm), and large (>200 nm) pegylated PHDCA nanoparticles incubated with serum protein for 2 h showed a significant correlation between particle size and protein absorption.Protein absorption on small nanoparticles (80 nm) was quantified (6%) and compared to the same nanoparticle formulation with a larger size (171 and 243 nm, 23 and 34%, respectively). The effect of protein absorption on different sized nanoparticles was also confirmed with the analysis of nanoparticle uptake by murine macrophages and blood clearance kinetics. Blood clearance of the smaller nanoparticles was twice as slow as with the larger nanoparticle formulations. More importantly, the amount of drug encapsulated (TNF-α) in nanoparticles that accumulated in the tumor within 24 h was twice that of the larger nanoparticle formulation.

In summary, it has been consistently shown that pegylated nanoparticles smaller than 100 nm have reduced plasma protein adsorption on their surface and also have reduced hepatic filtration. Further, these small pegylated nanoparticles have a long blood residence time and a high rate of extravasation into permeable tissues, demonstrating the importance of tunable particle size and surface composition for achieving effective, targeted delivery

3.2. Effect of the Core

3.3Effect of Surface Functionality and Charge

It has been established that the physicochemical characteristics of a polymeric nanoparticle such as surface charge and functional groups can affect its uptake by the cells of the phagocytic system. It was previously shown that polystyrene microparticles with a primary amine at the surface underwent significantly more phagocytosis as compared to microparticles having sulfate, hydroxyl, and carboxyl groups. Therefore, it is well accepted that positively charged nanoparticles have a higher rate of cell uptake compared to neutral or negatively charged formulations. Nanoparticles carrying a positively charged surface are also expected to have a high nonspecific internalization rate and short blood circulation half-life. Nanoshells having a negative surface charge have shown a marked reduction in the rate of uptake. The ζ potential for nanoshells with BSA absorbed on the surface of the nanoparticle was characterized by a shift to a more negative value. However, the BSA absorption did not promote a higher rate of cell uptaketer in controlling the developmen Thus; surface functionality is another critical parame t of long-circulating nanoparticles.

3.4 Effect of Active Targeting

Active targeting of nanoparticles involves the conjugation of targeting ligands to the surface of nanoparticles. These ligands can include antibodies, engineered antibody fragments, proteins, peptides, small molecules, and aptamers. The active targeting mechanism takes advantage of highly specific interactions between the targeting ligand and certain tissues or cells within the body to promote the accumulation of nanoparticles. In the case of weak binding ligands, low affinity can be offset by increased avidity through the surface functionalization of multiple molecules or multivalent designs and has been shown to be a valid approach. There are several examples of FDA-approved antibodies in clinical practice today, including Rituxan (target, CD20-positive B-cells for the treatment of non-Hodgkin’s lymphoma and rheumatoid arthritis), Herceptin (target, HER-2-overexpressing breast cancer cells), Erbitux [target, epidermal growth factor receptor (EGFR) for the treatment of colorectal cancer], Iressa (target, EGFR for the treatment of non-small cell lung cancer and metastatic breast cancer), and Avastin [target, vascular epidermal growth factor (VEGF) for the treatment of metastatic colorectal, non-small lung, and breast cancers]. While the progress with monoclocal antibodies has been encouraging, they have not been shown to be curative. Currently, drug delivery carriers are being functionalized with proteins, including antibodies or antibody fragments and various other targeting ligands, with the goal of both delivering a high therapeutic dose and delivering this high therapeutic dose to specific tissues or cells. Conjugation approaches for controlling the amount of targeting proteins on the surface of the nanoparticles have been developed to increase specificity and binding affinity. Research using proteins for targeting applications has led to a better understanding of the effect of stability and size of the ligand for successful targeting and clinical development. Cyclodextran-based nanoparticles containing transferrin targeting ligand (NP size of 70 nm) showed enhanced intracellular accumulation in a human tumor xenograft mouse model the discovery of new peptide targeting domains provides the advantage of being able to utilize small synthetic molecules for active targeting. One such example is peptides which are relatively stable compared to antibodies and are also less likely to be immunogenic. Similarly, small molecules can be very attractive for use as targeting ligands, and small molecules such as folic acid or sugar molecules have been extensively used. For example, cell surface membrane lectins have been shown to be overexpressed on the surface of numerous cancer cells and are able to specifically internalize sugar molecules (lactose, galactose, and mannose).Similarly, nucleic acid aptamers are able to fold into unique structures capable of binding to specific targets with high affinity and specificity.

Conclusion

The exact role of each of the proteins adsorbed on the surface of the nanoparticles in the clearance and biodistribution is still not clear besides their role in opsonization and enhanced hepatic uptake. It is generally assumed that the rapid uptake of injected nanoparticles is triggered by receptor-mediated mechanisms of absorbed proteins from the blood (opsonins) onto their surface and complement activation. However, it is not clear if a specific type, a combination of proteins, or even the protein conformation is the most important factor for a high rate of phagocytotic uptake. The efficacy of the PEG “brush” in altering the biodistribution of nanoparticles has been clearly demonstrated, and in vivo studies showed a drastic increase in blood circulation time with an increase in PEG surface density. Recently, targeted nanoparticles funtionalized with ligands that have high affinity and specificity have been shown to efficiently accumulate in specific tissues and dramatically increase the therapeutic efficacy of long-circulating nanoparticle drug delivery systems. Natural and synthetic polymers are now in preclinical and clinical phases for drug delivery. More importantly, targeted and nontargeted polymeric nanoparticles are now in the preclinical and clinical phases and confirm the great promise of the past 20 years of research and lessons learned from the failure of some clinical studies to increase the therapeutic index of drugs approved for clinical use.

4. Polymer used for preparation of nanoparticles

There are two polymers generally use in nanoparticle preparation

4.1. Natural hydrophilic polymer

4.2. Synthetic hydrophobic polymer

4.1. Natural hydrophilic polymer

Natural hydrophilic polymers are conveniently classified as protein and polysaccharide.

Various protein and polysaccharides used for the preparation of nanoparticles.

Protein-gelatin, albumin, lectins, legumin, vicilin etc.

Polysaccharide-alginate, dextran, chitosan, agarose, etc.

Note:-

Alginate based delivery systems for oral and ophthalamic administration have been aproved

In contrast, dextran, albumin, and gelatin which are though acceptable materials for parentral administration.

Disadvantage:-the polymer of natural origin suffer some disadvantage are-

Batch to batch variation

Conditional biodegradability

Antigenicity

Parentral administration of polymeric nanoparticle gets compromised mainly due to antigenicity.

4.2. Synthetic hydrophobic polymer

Most of them are typically hydrophobic in nature

The polymers are either pre-polymerised or synthesized before (first group) or during the (second group) process of nanoparticle preparation.

The polymer from the ester class polylactic acid and polylacticglycolic acid copolymer are representative of the first group along with poly caprolactoneand already been approved for humen use.

The second group is represented by poly (alkylcyanoacrylate), which have received the greatest attention as polymeric nanoparticle system but gathered number of controversies due to the toxicity of the corresponding alkylcyanoacrylate monomers.

Various synthetic polymers used for the preparation of nanoparticles

Pre-polymerised-poly (E-caprolactone), poly (lactic acid), poly (lactide-co-glycolide), polystyrene

Polymerised in process -poly (isobutylcyanoacrylate), poly (butylcyanoacrylate), poly (hexylcyanoacrylate), polymethyl (methacrylat)

Reason behind the formation of polymeric nanoparticle

Ø Administration of therapeutic agents has been limited by multiple factors such as low solubility, stability, and rapid clearance, the result is a short circulation half life and low efficacy, making frequent administration necessory. Additionally, there can be significant side-effect in non-diseased tissues that adsorbe therapeutic agent.

Ø These issues have led to the development of various targeting strategies aimed at increasing therapeutic index including monoclonal antibodiesand immunoconjugates.In addition to these strategies, it has been shown that polymer-drugconjugates can substantially improve the blood residence time and weaken side-effect.

Ø Many polymers have been investigated, including HPMA (N-(2-hydroxypropyl) methacrylamide, dextran and polyglutamate.

Ø HPMAand polyglutamate drug conjugates represent 35% of all the polymeric drug delivery system in clinical development. Thus, the main impact of polymeric conjugates has been to improve the pharmacokinetics parameters of drugs already in clinical use.

Ø These polymeric nanocarriers must be non-toxic, non-immunogenic and carry sufficient amount of drug and release the drug at the optimal dose.

5. Method of preparation

5.1. Amphiphilic macromolecules cross linking

5.1.1 Heat cross linking

5.1.2Chemical cross linking

5.2. Polymerization based method

5.2.1. Polymerization of monomers in-situ

5.2.2. Emulsion (micellar) polymerization

5.2.3. Dispersion polymerization

5.2.4. Interfacial condensation polymerization

5.2.5. Interfacial compexation

5.3. Polymer precipitation method

5.3.1. Solvent extraction/evaporation

5.3.2. Solvent displacement (nano precipitation)

5.3.3. Salting out

5.1. Preparation by cross-linking of amphiphilic macromolecules

Polymeric nanoparticle can be prepared from amphiphilic macromolecules, proteins and polysaccharide (which have affinity for aqueous and lipid solvents)

Aqueous protein

(BSA)

Macromolecular cross linking in water in oil (W/O) emulsion

Cross-linking in w/o emulsion

The cross linking method is exhaustively used for the nano-encapsulation of drugs.

The method involves the emulsification of bovin serum albumin (BSA)/human serum albumin (HAS) or protein aqueous solution in oil using high pressure homogenization or high frequency sonicatio

The water in oil emulsion formed

Then poured in to preheated oil (temp.above 100˚c)

Suspension in preheated oil maintained above (100˚c) is held stirred for a specific time in order to denature and aggregate the protein content of aq.pool completely

Evaporate the water

Proteinaceous subnanoscopic particle are formed Formed particles are washed with an organic solvent to remove any adherent or absorbed oi and subsequently collected by centrifugation

Polymers used for the preparation of nanoparticle

Polymer Used Technique Candidate Drug

1. Hydrophilic

Eg: albumin and heat denaturation and cross linking in hydrophilic

Gelatin w/o emulsion

desolvation and cross linking in aq. hydrophilic and

Medium protein affinity

Alginate, chitosan cross-linking in aq.medium hydrophilic and

Protein affinity

Dextran polymer precipitation in an hydrophilic

Organic solvent

2. Hydrophobic

Eg: poly (alkylcyanoacrylate) emulsion polymerization hydrophilic

interfacial o/w polymerization hydrophobic

3. Polyesters: eg

Poly lactic acid solvent extraction/evaporation hydrophilic and hydrophobic

, polylactide-co-glycolide solvent displacement soluble in polar solvent

Poly (E-caprolactone) salting out soluble in polar solvent

5.2. Preparation of PNP using polymerization based method

5.2.1. Polymerization of monomer in-situ

Preparation of polymeric nanoparticles mainly discusses in-situ emulsion technique.

Polymers used for nanospheres preparation include poly (methylmethacrylate), poly (acrylamide),

Poly (butylcyanoacrylate), n, n-methylene-bis-acryl-amide etc.

Two different approaches are generally adapted for the preparation of nanospheres using insitu polymerisation technique

5.2.1.1. Method in which the monomer to be polymerise is emulsified in a non solvent phase (emultion polymerisation)

5.2.1.2. Method in which the monomer is dissolved in a solvent that is non solvent for resulting polymer (dispersion polymerisation)

5.2.2. Emulsion polymerisation

Two different mechanism were proposed for the emulsion polymerisation process and they include

5.2.2.1. Micellar nucleation and polymerisation

5.2.2.2. Homogenous nucleation and polymerisation

Micellar nucleation and polymerisation

Step 1-swollen monomer micelles at the site of nucleation and polymerisation

The monomer is emulsified in the non solvent phase with the help of surfactant molecule

Formation of monomer swollen micelle and stabilise monomer droplet

Swollen micelle exhibit sizes in the nanometric range and thus has a much larger surface area in comparision to monomer droplet

Step 2-

The polymerisation reaction proceeds through nucleation and propagation stage in the presence of chemical or physical initiator

The energy provide by the initiator creates free reactive monomers in the continuous phase which then collide with surrounding unreactive monomer and initiate the polymerisation chain reaction

Being slightly soluble in the sorrounding phase the monomer mollecules reach the micelle by diffusion from the monomer droplet through the continuous phase thus allowing the polymerisation to progress within the micelles therefore in this case the monomer droplet essentially act as monomer reservoir.

Preparation of poly alkylcyanoacrylate (paca) nanoparticles using emulsion polymerization

Mechanical stirring

Poly nanosphere poly nanocapsule

**for lipophilic drug:-

Mixture of polar solvent =methanol/acetone

Oil=benzylbenzoate, coconut oil

Lipophilicsurfactant=lecithin

5.2.3. Dispersion polymerization

The term emulsion polymerization is used when the monomer is emulsified in an immiscible (non-solvent) phase by means of surfactant.

In case of dispersion polymerization however, the monomer instead of being emulsified, is dissolved in an aq.medium which acts as a precipitant for subsequent formed polymer.

Polymerization based method essentially involves in-situ controlled polymerization of appropriate monomer where drug may be added to monomeric phase or may be added to the formed polymeric nanoparticulate dispersion for adsorptive loading.

The monomer is introduced in to the dispersion medium (phase) of an emulsion or an inverse emulsion in to non-solvent based polymeric solution.

Polymerization is initiated by adding a catalyst and proceeds with nucleation phase followed by a growth phase (propagation).

On the other hand, in the case of dispersion polymerization, the nucleation is directally induced in the aq.monomer solution and the persence of stabilizers or surfactant is not absolutely necessary for the formation of stable nanospheres.

5.2.4. Interfacial polymerization

In this method, the preformed polymer phase is finally transformed to an embryonic sheath.

A polymer that eventually becomes core of nanoparticle and drug molecules to be loaded are dissolved in a volatile solvent.

The solution is then poured in to a non-solvent for both polymer and core phase.

The polymer phase is separated as a coacervate phase at o/w interface.

The resultant mixture instantaneously turns milky owing to the formation of nanocapsules.

The solvent is subsequently removed undervacuum

Polymer phase

Core phase+drug

The size of nanocapsules ranges from 30-300nm and drug loading efficiency depends on drug solubility in core phase.

Core phase+dr polymer p

Core dispersed in polymer

Phase (O/W emulsion)

Add non-solvent, which precipitate out polymer

From either of phases and solvent is

Subsequently removed under vacuum

Polymeric nanocapsules

(30-300nm)

5.2.5. Interfacial complexatio

The method is based on the process of microencapsulation. In the case of polymeric nanoparticle preparation, aq. Polyelectrolyte solution is carefully dissolved in reverse micelles in an apolar bulk phase with the help of an appropriate surface active agent.subsequently, competing polyelectrolyte is added to the bulk which allows a layer of insoluble polyelectrolyte complex to coacervate at the interface.

5.3. Nanoparticle preparation using polymer precipitation method

In this method, hydrophobic polymer (dextran, mainly polyesters) orhydrophobic drug is dissolved in a particular organic solvent followed by its dispersion in a continuous aq.phase in which the polymer is insoluble.

The external phase also contains the stabilizers.

Depending upon solvent miscibility techniques they are designated as solvent extraction/evaporation method

The polymer precipitation occurs as a consequence of the solvent extraction or evaporation.

Stirred properly

Then dispersion in a continuous phase in which polymer is insoluble

5.3.1. Solvent extraction/evaporation method

Sonication/homogenizatio

O/W emulsion

Solvent extraction/evaporation

Polymeric nanoparticle is formed

This method involves the formation of a conventional o/w emulsion between a partially water miscible solvent containing the polymer, drug, and an aq.phase containing stabilizer.

The subsequent removal of solvent (solvent evaporation method) with high speed /pressure homogenization.

The homogenizer breaks the initial coarse emulsion in nanodroplets (nanofluidizatio) yielding nanospheres with a narrow size distribution.

Double emulsion solvent evaporation method

Sonication/homogenization

W/O emulsion stabilized at 4®c

Add aqueous phase with stabilizer (polyvinylalcohol)

W/O/W emulsion

Solvent extraction/solvent evaporation

Polymeric nanoparticle is formed

Aqueous phase

Distilled water, poloxamer 188

Organic phase

Solvent, polymer, drug

5.3.2. Solvent displacement or nano precipitation

Magnetic stirring

Polymeric nanospheres

Aqueous phase

Distilled water, poloxamer 188

Organic phase

Polar solvent, oil, polymer, drug

Magnetic stirring Polymeric nanospheres

Polymeric nanosphere is formed

5.3.3. Salting out method

This technique is suitable for drug and polymers that are soluble in polar solvent.

In this technique, the miscibility of both phases is prevented by the saturation of the external aq. Phase with polyvinylalcohol.

The precipitation of the polymer occurs when a sufficient amount of water is added to the external phase to allow coplete diffusion of the acetone from internal phase in to aq. Phase.

Aqueous phase

Distilled water, polyvinylalcohol,

Magnesiumchloride

Organic phase

Organic solvent, drug, polymer

Mechanical stirring

O/W emulsion

Add distilled water (precipitation occurs)

Polymeric nanoparticles is formed

6. Evaluation and characterization parameter of polymeric nanoparticle

6.1. Size and morphology

The particle size is one of the most important parameters of polymeric nanoparticles.

There are two techniques generally used to determine the particle size distribution of polymeric nanoparticle

Photon correlation spectroscopy (pcs)

Electron microscopy

The scanning electrone microscopy (SEM), transmission electron microscopy (TEM) and freeze-fracture techniques are used.

6.2. Density

The density of polymeric nanoparticles is determined with helium or air using a gas pycnometer.

The value obtained with air and with helium is much more pronounced due to the specific surface area and porosity of the structure.

6.3. Surface charge and electrophoretic mobility

The nature and intensity of the surface charge of polymeric nanoparticle is very important as it determines their interaction with the biological environment as well as their electrostatic interaction with bioactives compounds.

The surface charge of colloidal particles could be measured by electrophoretic mobility.

Generally the electrophoretic mobility of polymeric nanoparticle is determined in phosphate saline buffer (pH=7.4) and human serum.

Phosphate buffer solution (pH=7.4) relatively reduce the absolute charge value due to ionic interaction of buffer components with the charged surface of polymeric nanoparticle

6.4. Surface hydrophobicity

The surface hydrophobicity of polymeric nanoparticle has an important influence on the interaction of colloidal particles with the biological environment (eg.protein adsorption and cell adhesion)

The hydrophobicity and hydrophilicity collctively determine the bio-fate of nanoparticles and their content.

The hydrophobicity regulates the extent and type of hydrophobic interactions of nanoparticulates with blood component.

Several methods including –

-Hydrophobic interaction chromatgraphy

-Two phase partition

-Adsorption of hydrophobic fluorescent or radiolabelled probes

-Contact angle measurement

6.5. Specific surface

The specific surface area of freeze –dried polymeric nanoparticle is generally determined by the help of sorptometer

A= 6

σ xḍ

The equation given below can be used in the calculation of specific surface area.

A=specific surface area, σ=density, d=diameter of the particle

6.6. Molecular weight measurements of nanoparticle -molecular weight of the polymer and its distribution in the matrix can be evaluated by gel permeation chromatography (GPC) using a refractive index detector.

6.7. Nanoparticle recovery and drug incorporation

Concentration of drug in polymeric nanoparticle %Nanoparticles recovery = x100 or drug content Concentration of polymeric nanoparticle

6.8. In vitro release

In vitro release profile can be determined using standard dialysis, diffusin cell or recently introduced modified ultrafiltration technique.

In vitro drug release from the polymeric nanoparticles can be evaluated in phosphate buffer utilizing double chamber diffusion cells on a shaker stand

A millipore hydrophilic low-protein binding membrane is placed between the two chambers.

The donar chamber is filled with polymeric nanoparticulate suspension and the receiver chamber with plain buffer.

The receiver compartment is assayed at different time intervals for the released drug using standard procedure.

Magenheim and co-workers, 1993 used a modified ultrafiltration technique to determine in vitro release behaviour of the PnP suspension.

The PnP suspension is added directly in to a stirred ultrafiltration cell containing buffer.

At different time interval aliquots of the dissolution medium are filtered through the ultrafiltration membrane using less than two bars positive nitrogen pressure and assayed for the released drug using standard procedures.

7. Application of polymeric nanoparticles

7.1. Cancer therapy-

Material used-: poly (alkylcyanoacrylate)

Purpose-: targeting, reduced toxicity, enhanced uptake of antitumour agents, improve in-vitro and in-vivo stability.

7.2. Intracellular targeting-

Material used-: poly (alkylcyanoacrylate), polyesters with anti-parasitic or antiviral agent.

Purpose-: target reticuloendothelial system for intracellular infection.

7.3. Prolonged systemic circulation-

Material used-: polyesters with adsorbed polyethylene glycolor pluronic or derivatized polymer.

Purpose-: prolonged systemic drug effect, avoid uptake by the reticuloendothelial system.

7.4. Vaccine adjuvant-

Material used-: poly (methylmethacrylate) nanoparticle with vaccine (oral and intramuscular immunization).

Purpose-: enhances immune response, alternate acceptable adjuvant.

7.5. Peroral adsorption-

Material used-: poly (methylmethacrylate) nanoparticle with protein and therapeutic agent.

Purpose-: enhanced bioavailability, protection from gastrointestinal enzymes.

7.6. Ocular delivery-

Material used-: poly (methylmethacrylate) nanoparticle with steroids, anti-inflammatory agents, anti-bacterial agentfor glucoma.

Purpose-: improve retention of drug/reduced wash out.

7.7. DNA delivery-

Material used-: DNA-gelatin nanoparticles, DNA-chitosan nanoparticle, PDNA-poly (DL-lactide-co-glycolide) nanoparticles.

Purpose-: enhanced delivery and significantly higher expression levels.

7.8. Oligonucleotide delivery-

Material used-: alginate nanoparticle, poly (D, L) lactic acid nanoparticle.

Purpose-: enhanced delivery of oligonucleotides.

7.9. Other application-

Material used-: poly (alkylcyanoacrylate) nanoparticle with peptides.

Purpose-: crosses blood –brain barriers.

Material used-: poly (alkylcyanoacrylate) nanoparticle for transdermal application.

Purpose-: improve absorption and permeation.

Material used-: nanoparticles with adsorbed enzymes.

Purpose-: enzyme immunoassay.

Material used-: nanoparticles with radioactive or contrast agent.

Purpose-: radio-imaging.

Other than pharmaceutical uses

· Waterborne paint

· Adhesive

· Coating

· Redispersible latices

· Powder coatings

· Pressure sensitive adhesives

· Hot melts

· Biotechnology

· Biomedical products

· Drug delivery

· Medical diagnostics

· Problem solving

· Electronics

· Magnetics

· Optoelectronics

8.Patent and marketed product

Clinical Status of Polymeric Drug Delivery Nanoparticles under Development

composition (trade name)	status	particle size (nm)	circulation half-life	relative tissue accumulation of the drug	maximum tolerated dose (MTD)	efficacy
methoxy-PEG-poly(d,l-lactide)Taxol (Genexol-PM)	Phase II	30−60 nm	paclitaxel, 12 h (human)	Genexol-PM vs Taxol: 2× more in liver, spleen, heart, and tumor (mice)	390 mg/m²administered intravenously for 3 h every 3 weeks (human)	75% of metastatic breast cancer patient showed 2 years overall survival
HPMA-DACH palatinate (ProLindac, previously AP5346)	Phase II	6−15 nm	DACH-platinum, 70 h (human)	NA^a	640 mg/m² (initial cycle); repeated cycles of therapy were not assessed (human)	NA^a
PEG-arginine deaminase (Hepacid, previously ADI-SS PEG 20000 MW)	Phase I/II	NA^a	arginine deaminase, 7 days (human	NA^a	640 units/m² once a week (MTD > maximum feasible dose by intravenous (iv) administration)	double median survival time of patients with metastatic melanoma; 47% response rate in HCC patients (n = 19)
PEG-camptothecin (Prothecan)	Phase I/II	NA^a	camptothecin, 40 h (human)	camptothecin % ID/g of tissue 24 h postinjection: 3.7% in tumor, 4.41% in blood, 2.32% in liver (mice)	7000 mg/m²administered in 1 h iv infusions every 3 weeks (human)	NA^a
Pluronic-doxorubicin (SP1049C)	Phase II	25 nm	doxorubicin, 3 h (human)	enhanced AUC in tumor (50.8 vs 30.1) and brain (9.2 vs 5.6) compared with free doxorubicin (mice)	70 mg/m²administered intravenously every 3 weeks for a maximum of six cycles (human)	three patients over 21 showed responses to treatment
polycyclodextrin camptothecin (IT-101)	Phase I	40 nm	camptothecin, 38 h (mice)⁷¹	camptothecin % ID/g of tissue: tumor = 1.3%; liver = 1.9% (24 h) (mice)	NA^a	preliminary data is reported to show stable disease rate in patients with solid tumor
polyglutamate camptothecin (CT-2106)	Phase I/II	NA^a	camptothecin, 44−63 h (human)	NA^a	25 mg/m²administered by iv infusion weekly every 3 of 4 weeks (human)	less toxicity than free dru
polyglutamate paclitaxel (Xyotax)	Phase III	NA^a	paclitaxel, 100 h (human)	paclitaxel % ID/g of tissue: tumor = 2.2%; spleen = 16%; liver = 8% (mice)	for an iv administration, 233 mg/m² for patients on a two-dose weekly schedule and 177 mg/m² on a three-dose weekly schedule (human)	response rate of 10% for 99 patients and a median time to disease progression of 2 months
dextran-doxorubicin (AD-70)	Phase I	NA^a	doxorubicin, 3−12 h (human)	NA^a	20 mg/m²(human)	discontinued due to severe hepatotoxicity limiting the dose at 20 mg/m²
dextran-camptothecin (DE-310)	Phase I/II	NA^a	camptothecin, 300−400 h (human)	NA^a	9 mg/m² given once every 4 weeks (human)	no new major toxicity compared to drug beside hepatotoxicity reported as reversible
HPMA-paclitaxel (PNU166945)	Phase I	NA^a	paclitaxel, 3−12 h (huma	NA^a	196 mg/m²(human)	discontinued due to severe neurotoxicity
HPMA-doxorubicin (PK1)	Phase II	NA^a	doxorubicin, 93 h (human)	NA^a	320 mg/m²(human)	hepatic toxicity at doses > 120 mg/m²; two partial and two minor responses over 36 patient
PEG-aspartic acid-doxorubicin (NK911)	Phase I	30−50 nm	doxorubicin, 1.6−4.7 h (human)		67 mg/m², plasma clearance 400-fold higher than Doxil (human)	no severe toxicity; Phase II clinical trial for pancreatic cancer
HPMA-doxorubicin with galactosamine (PK2)	Phase I	8.4 nm	biphasic clearance with half-lives of 2.9 and 26.7 h when 120 mg/m²administered by 24 h infusion (human)	enhanced accumulation in liver, hepatoma, and metastatic hepatoma compared with nontargeted HPMA-doxorubicin (human	160 mg/m² with administration by iv infusion over 1 h every 3 weeks (human)	of 18 patients, three responded to treatment, with two in partial remission for >26 and >47 month

9. Recent development in polymeric nanoparticle

9.1 Recent Developments in Polymeric Nanoparticle Engineering and Their Applications in experimental and Clinical Oncology

Promising results have come from attempts to direct drugs, nucleic acids and diagnostic agents to tumours by using polymeric nanoparticles. Such carriers are versatile; their encapsulation capacity, drug release profile, and biological performance vary with their chemical makeup, morphology, and size. Polymeric nanoparticles may therefore be engineered for therapeutic and diagnostic purposes in accordance with the type, developmental stage and location of the cancer as well as the required route of administration. This article examines recent developments in design and engineering of polymeric nanoparticles and related platforms to include supramolecular systems such as nanocapsules and nanoparticlebased hydrogels, and assesses their potential diagnostic and therapeutic applications in experimental and clinical oncology.

9.2 Nanotechnology has the potential to revolutionize cancer diagnosis and therapy.

Advances in protein engineering and materials science have contributed to novel nanoscale targeting approaches that may bring new hope to cancer patients. Several therapeutic nanocarriers have been approved for clinical use. However, to date, there are only a few clinically approved nanocarriers that incorporate molecules to selectively bind and target cancer cells. This review examines some of the approved formulations and discusses the challenges in translating basic research to the clinic. We detail the arsenal of nanocarriers and molecules available for selective tumour targeting, and emphasize the challenges in cancer treatment.

9.3 Layer-by-Layer Growth of Polymer/Nanoparticle Films Containing Monolayer-Protected Gold Clusters:-

Multilayer films of nanoparticles were grown in a systematic and controlled manner layer-by-layer by alternating exposures of suitably functionalized substrates (glass, Au) to either poly(allylamine) and carboxylic acid-functionalized nanoparticles or to poly(styrene sulfonate) and arylamine-functionalized nanoparticles. Electrostatic interactions comprise the dominant film growth factors. The rate of multilayer film growth depends on the polymer solution pH and other details of the solution exposures. Growth was followed by spectrophotometry of the Au nanoparticle cores, voltammetry of the Au core double layer charging, and film mass (quartz crystal microbalance). The first example is reported of quantized double layer charging of the Au cores in a layer-by-layer film that is composed of monolayer-protected clusters and a polyelectrolyte.

9.4 Recent developments in ophthalmic drug delivery

Recent research efforts in ophthalmic drug delivery have mainly focused on systems in which drugs may be administered in the form of eye-drops. As a result of these efforts, significant advancements have been made in the following areas: in situ-forming gels, oil-in-water emulsions, colloidal drug delivery systems (liposomes and nanoparticles) and microparticulates. Protein and peptide delivery, posterior drug delivery and non-aqueous vehicles are three new areas of interest in ophthalmic drug delivery, and this review will discuss recent progress and specific development issues relating to these drug delivery systems

10. References

Cristina Buzea, Ivan Pacheco, and Kevin Robbie (2007). Nanomaterials and Nanoparticles: Sources and Toxicity,Biointerphases 2 (4): MR17-MR71.
ASTM E 2456 – 06 Standard Terminology Relating to Nanotechnology
Fahlman, B. D. (2007). Materials Chemistry. Springer. pp. 282–283.
A.B.D. Nandiyanto; S.-G Kim; F. Iskandar; and K. Okuyama 2009 447–453
Philip S. Rawson (1984). Ceramics. University of Pennsylvania Press
Faraday, Michael (1857). Experimental relations of gold (and other metals) to light, Phil. Trans. Roy. Soc.
Whitesides, G.M., et al. (1991). "Molecular Self-Assembly and Nanochemistry: A Chemical Strategy for the Synthesis of Nanostructures". Science 254: 1312
Robert Corriu, Nguyên Trong Anh (2009). Molecular Chemistry of Sol-Gel Derived Nanomaterials. John Wil
Agam, M. A.; Guo, Q (2007). "Electron Beam Modification of Polymer Nanospheres". Journal of Nanoscience and Nanotechnology 7 (10): 3615
Vyas SP.and Khar RK.Targeted and controlled drug delivery, First-edition, CBS publishers and distributors, page no.331-381.
Jain NK.Controlled and novel Novel Drug Delivery,First-edition, cbs publishers and distributors, page no.93

niosome

2010-12-08T10:14:00.001-08:00

NIOSOME ( as a drug carrier)
1. Introduction:-
1.1. Historical aspect-
Niosomes were first reported in the seventies as a feature of the cosmetic industry by Vanlerberghe et al, Handjani-vila et al., Van Abbe explained that the non – inonic surfactants are preferred because the irritation power of surfactants decreases in the following order: cationic > anionic > ampholytic > non-ionic. Green and Downs, Keller et al., Burstein, Kaur and Smitha reported that an increased ocular bioavailability of water soluble, entrapped in niosomes, may be due to the fact that surfactants also act as penetration enhancers as they can remove the mucus layer and break functional complexes. Handjani-Vila et al. reported that vesicular systems were formed when a mixture of cholesterol and single alkyl chain, non-ionic surfactants was hydrated. The resultant vesicles, termed as niosomes can entrap solute. Okhata et al. suggested vesicle formation by some members of dialkylpoly oxyethlene ether non-ionic surfactant series. Singh and Mezei stated that niosomes are a suitable delivery system for both hydrophilic and lipophilic drugs. Baillie et al.reported that niosomes are osmotically active and relatively stable. Lasicstated that the assembly into closed bilayers is rarely spontaneous and usually involves some input of energy such as physical agitation or heat. The result is an assembly in which the hydrophobic parts of the molecule are shielded from the aqueous solvent and the hydrophilic head groups enjoy maximum contact with same. The non-ionic surfactant vesicles have been reported successfully by Saettone et al. as ocular vehicle for cyclopentolate. Carafa et al. stated that niosomes are the non-ionic surfactant vesicles and like liposomes are bilayered structures, which can entrap both hydrophilic and lipophillic drugs either in an aqueous layer or in vesicular membrane, made up of lipids. Vyas et al.prepared both niosomes and discomes of water-soluble drug timolol maleate and found that discomes entrapped comparatively a higher amount of drug (25% as compared to 14% in case of niosomes). Moreover, an increase in ocular bioavailability was found to be approximately 3.07-fold compared to 2.48-fold in case of niosomes with respect to timolol maleate solution. Carafe et al.reported that niosomes are biodegradable, biocompatible, and non-immunogenic. Indu P. Kaur et al. gave an impression on vesicular system in ocular drug delivery. Deepika Aggarwal et al. studied the improved pharmacodynamics of timolol maleate from a mucoadhesive niosomal ophthalmic drug delivery system. Deepika Aggarwal et al. studied the ocular absorption of acetazolamide by microdialysis sampling of aqueous humor. Ghada abdelbary and Nashwa el-gendy investigated the feasibility of using non-ionic surfactant vesicles as carriers for the ophthalmic controlled delivery of a water soluble local antibiotic, Gentamicin sulphate.
At present no available drug delivery system achieves the site specific delivery with controlled release kinetics of drug in predictable manner.
Paul Ehrlich, in 1909, initiated the era of development for targeted delivery when he envisaged a drug delivery mechanism that would target directly to diseased cell. Since then, number of carriers was utilized to carry drug at the target organ/tissue, which include immunoglobulins, serum proteins, synthetic polymers, liposomes, microspheres, erythrocytes, niosomes etc.
Among different carriers liposomes and niosomes are well documented drug delivery.
Drug targeting can be defined as the ability to direct a therapeutic agent specifically to desired site of action with little or no interaction with nontarget tissue.
Niosomes or non-ionic surfactant vesicles are microscopic lamellar structures formed on admixture of non-ionic surfactant of the alkyl or dialkyl polyglycerol ether class and cholesterol with subsequent hydration in aqueous media.
In niosomes, the vesicles forming amphiphile is a non-ionic surfactant such as Span – 60 which is usually stabilized by addition of cholesterol and small amount of anionic surfactant such as dicetyl phosphate.
1.2. Definition:-
Niosomes are non-ionic surfactant vesicles obtained on hydration of synthetic nonionic surfactants, with or without incorporation of cholesterol or other lipids.They are vesicular systems similar to liposomes that can be used as carriers of amphiphilic and lipophilic drugs. Niosomes are promising vehicle for drug delivery and being non-ionic; it is less toxic and improves the therapeutic index of drug by restricting its action to target cells. This systemic review article deals with preparation methods, characterizations, factors affecting release kinetic, advantages, and applications of niosomes. Schematic representation of a drug targeting through its linkage to niosome via antibody is shown in figure 1-

Figure 1: Niosome structure

Figure 2: Niosome structure

1.3. Advantages of niosomes:-

They entrap solute in a manner analogous to liposomes.
They are osmotically active and stable.
Handling and storage of surfactants requires no special conditions.
They possess an infrastructure consisting of hydrophobic and hydrophilic moieties together and as a result can accommodate drug molecules with a wide range of solubilities.
They exhibit flexibility in their structural characteristics (composition, fluidity, and size) and can be designed according to desired application.
They improve oral bioavailability of poorly absorbed drugs and enhance skin penetration of drugs.
They allow their surface for attachment of hydrophilic group and can incorporate hydrophilic moieties in bilayer to bring about changes in their in vivo behavior.
The surfactants are biodegradable, biocompatible, and nonimmunogenic.
They improve the therapeutic performance of the drug molecules by delaying the clearance from the circulation, protecting the drug from biological environment, and restricting effects to target cells.
Niosomal dispersion in an aqueous phase can be emulsified in a nonaqueous phase to regulate the delivery rate of drug and administer normal vesicle in external nonaqueous phase.

2. Types of niosomal system:-
2.1. Small unilamellar vesicles- (SUV, size -0.025-0.05 μm) are commonly produced by sonication, and French Press procedures. Ultrasonic electrocapillary emulsification or solvent dilution techniques can be used to prepare SUVs.
2.2. Multilamellar vesicles- (MLV, size >0.05 μm) exhibit increased-trapped volume and equilibrium solute distribution, and require hand-shaking method. They show variations in lipid compositions.
2.3. Large unilamellar vesicles- (LUV, size >0.10 μm), the injections of lipids solubilised in an organic solvent into an aqueous buffer, can result in spontaneous formation of LUV. But the better method of preparation of LUV is Reverse phase evaporation, or by Detergent solubilisation method.
3. Factors affecting formation of niosomes:-
a)   Drug-
Entrapment of drug in niosomes increases vesicle size, probably by interaction of solute with surfactant head groups, increasing the charge and mutual repulsion of the surfactant bilayers, thereby increasing vesicle size. In polyoxyethylene glycol (PEG) coated vesicles; some drug is entrapped in the long PEG chains, thus reducing the tendency to increase the size^.The hydrophilic lipophilic balance of the drug affects degree of entrapment.
b)   Amount and type of surfactant-
The mean size of niosomes increases proportionally with increase in the HLB of surfactants like Span 85 (HLB 1.8) to Span 20 (HLB 8.6) because the surface free energy decreases with an increase in hydrophobicity of surfactant.
The bilayers of the vesicles are either in the so-called liquid state or in gel state, depending on the temperature, the type of lipid or surfactant and the presence of other components such as cholesterol. In the gel state, alkyl chains are present in a well-ordered structure, and in the liquid state, the structure of the bilayers is more disordered. The surfactants and lipids are characterized by the gel-liquid phase transition temperature (TC). Phase transition temperature (TC) of surfactant also effects entrapment efficiency i.e. Span 60 having higher TC, provides better entrapment.
c)   Cholesterol content and charge-
Inclusion of cholesterol in niosomes increases its hydrodynamic diameter and entrapment efficiency. In general, the action of cholesterol is two folds; on one hand, cholesterol increases the chain order of liquid-state bilayers and on the other, cholesterol decreases the chain order of gel state bilayers. At a high cholesterol concentration, the gel state is transformed to a liquid-ordered phase.
An increase in cholesterol content of the bilayers resulted in a decrease in the release rate of encapsulated material and therefore an increase of the rigidity of the bilayers obtained. Presence of charge tends to increase the interlamellar distance between successive bilayers in multilamellar vesicle structure and leads to greater overall entrapped volume.
d)   Methods of preparation-
Methods of preparation of niosomes such as hand shaking, ether injection and sonication have been reviewed by Khandare et al. Hand shaking method forms vesicles with greater diameter (0.35-13nm)compared to the ether injection method (50-1000nm).
Small sized niosomes can be produced by Reverse Phase Evaporation (REV) method .Microfluidization method gives greater uniformity and small size vesicles. Parthasarthi et al prepared niosomes by Trans membrane pH gradient (inside acidic) drug uptake process. Niosomes obtained by this method showed greater entrapment efficiency and better retention of drug.

e.) Nature of surfactants-
A surfactant used for preparation of niosomes must have a hydrophilic head and hydrophobic tail. The hydrophobic tail may consist of one or two alkyl or perfluoroalkyl groups or in some cases a single steroidal group. The ether type surfactants with single chain alkyl as hydrophobic tail is more toxic than corresponding dialkylether chain. The ester type surfactants are chemically less stable than ether type surfactants and the former is less toxic than the latter due to ester-linked surfactant degraded by esterases to triglycerides and fatty acid in vivo. The surfactants with alkyl chain length from C12-C18 are suitable for preparation of niosome. Surfactants such as C16EO5 (poly-oxyethylene cetyl ether) or C18EO5 (polyoxyethylenesteryl ether) are used for preparation ofpolyhedral vesicles.Span series surfactants having HLB number of between 4 and 8 canform vesicles.

f.) Structure of surfactants-
The geometry of vesicle to be formed from surfactants isaffected by its structure, which is relatedto critical packingparameters. On the basis of critical packing parameters ofsurfactants canpredicate geometry of vesicle to be formed.Critical packing parameters can be defined usingfollowingequation,

Where v = hydrophobic group volume,
lc = the critical hydrophobic group length,
a0 = the area of hydrophilic head group.
From the critical packing parameter value type ofmiceller structure formed can be ascertained as given below,
If CPP < ½ then formation of spherical micelles,
If ½ < CPP < 1 formation of bilayer micelles, &
If CPP > 1 formation inverted micelles.

g.) Membrane composition-
The stable niosomes can be prepared with addition ofdifferent additives along with surfactants and drugs.Niosomes formed have a number of morphologies andtheir permeability and stability properties can be altered bymanipulating membrane characteristics by differentadditives. In case of polyhedral niosomes formed from C16G2, the shape of these polyhedral niosome remains
unaffected by adding low amount of solulan C24 (cholesteryl poly-24-oxyethylene ether), which preventsaggregation due to development of steric hindrance. In contrast sphericalniosomes are formed by C16G2: cholesterol: solulan (49:49:2) 2000).The mean size ofniosomes is influenced by membrane composition such as polyhedral niosomes formed by C16G2: solulan C24 in ratio(91:9) having bigger size (8.0 ± 0.03mm) thanspherical/tubular niosomes formed by C16G2:cholesterol:solulan C24 in ratio (49:49:2) Addition of cholesterolmolecule to niosomal system provides rigidity to themembrane and reduces the leakage of drug from niosome.

h.) Nature of encapsulated drug-
The physico-chemical properties of encapsulated druginfluence charge and rigidity of the niosome bilayer. Thedrug interacts with surfactant head groups and develops thecharge that creates mutual repulsion between surfactantbilayers and hence increases vesicle size (Stafford S et al., 1988). The aggregation of vesicles is prevented due to the charge development on bilayer.

i.) Temperature of hydration-
Hydration temperature influences the shape and size of thenoisome. For ideal condition it should be above the gel to liquid phase transition temperature of system. Temperaturechange of niosomal system affects assembly of surfactantsinto vesicles and also induces vesicle shape transformation. Arunothayanun et al. reported that a polyhedral vesicleformed by C16G2: solulan C24 (91:9) at 25°C which on heating transformed into spherical vesicle at 48°C, but oncooling from 55°C, the vesicle produced a cluster ofsmaller spherical niosomes at 49°C before changing to the polyhedral structures at 35°C. In contrast vesicle formed by C16G2: cholesterol:solulanC24(49:49:2) shows no shape transformation onheating or cooling Along with the above mentioned factors, volume of hydration medium and time of hydration of niosomes arealso critical factors. Improper selection of these factorsmay results in formation of fragile niosomes or creation ofdrug leakage problems.

j.) Type of Surfactants-
Type of the surfactants influences encapsulation efficiency, toxicity, and stability of niosomes. The first niosomes were formulated using cholesterol and single-chain surfactants such as alkyl oxyethylenes. The alkyl group chain length is usually from C12–C18. The hydrophilic- lipophilic balance (HLB) is a good indicator of the vesicle forming ability of any surfactant. Uchegbu et al reported that the sorbitan monostearate (Span) surfactants with HLB values between 4 and 8 were found to be compatible with vesicle formation. Polyglycerol monoalkyl ethers and polyoxylate analogues are the most widely used single-chain surfactants.However, it must be noted that they possess less encapsulation efficiency in the presence of cholesterol. Etheric surfactants have also been used to form niosomes. These types of surfactants are composed of single-chain, monoalkyl or dialkyl chain. The latest ones are similar to phospholipids and possess higher encapsulation efficiency. Esther type amphyphilic surfactants are also used forniosome formulation. They are degraded by estherases, triglycerides and fatty acids. Although these types of surfactants are less stable than ether type ones, they possess less toxicity. Furthermore, glucosides of myristil, cethyl and stearyl alcohols formniosomes.
k.) Surfactant/Lipid and Surfactant/Water Ratios-
Other important parameters are the level of surfactant/lipid and the surfactant/water ratio. The surfactant/lipid ratio is generally 10–30 mM (1–2.5% w/w). If the level of surfactant/lipid is too high, increasing the surfactant/lipid level increases thetotal amount of drug encapsulated. Change in the surfactant/water ratio during the hydration process may affect the system's microstructure and thus, the system's properties.

l.) Other Additives-
As is the case with liposomes, charged phospholipids such as dicethylphosphate (DCP) and stearyl amine (SA) have been used to produce Charge in niosome formulations. The former molecule provides negative charge to vesicles whereas the later one is used in the preparation of positively charged (cationic) niosomes.

m.) Nature of the Drug-
One of the overlooked factors is the influence of the nature of the encapsulated drug on vesicle formation (Table 1). The encapsulation of the amphipathic drug doxorubicin has been shown to alter the electrophoretic mobility of hexadecyl diglycerol ether (C16G2) niosomes in a pH dependent manner, indicating that the amphipathic drug is incorporated in the vesicle membrane.
n.) Resistance to osmotic stress-
Addition of a hypertonic salt solution to a suspension of niosomes brings about reduction in diameter. In hypotonic salt solution, there is initial slowrelease with slight swelling of vesicles probably due to inhibition of eluting fluid from vesicles, followed by faster release, which may be due to mechanical loosening of vesicles structure under osmotic stress.
4. Method of prepration:-

4.1. Technique-

a.) Ether injection method-

This method provides a means of making niosomes by slowly introducing a solution of surfactant dissolved in diethyl ether into warm water maintained at 60°C. The surfactant mixture in ether is injected through 14-gauge needle into an aqueous solution of material. Vaporization of ether leads to formation of single layered vesicles. Depending upon the conditions used, the diameter of the vesicle range from 50 to 1000 nm.

b.) Hand shaking method (Thin film hydration technique)-

The mixture of vesicles forming ingredients like surfactant and cholesterol are dissolved in a volatile organic solvent (diethyl ether, chloroform or methanol) in a round bottom flask. The organic solvent is removed at room temperature (20°C) using rotary evaporator leaving a thin layer of solid mixture deposited on the wall of the flask. The dried surfactant film can be rehydrated with aqueous phase at 0-60°C with gentle agitation. This process forms typical multilamellar niosomes. Thermosensitive niosomes were prepared by Raja Naresh et al by evaporating the organic solvent at 60°C and leaving a thin film of lipid on the wall of rotary flash evaporator. The aqueous phase containing drug was added slowly with intermittent shaking of flask at room temperature followed by sonication.

c.) Sonication-

A typical method of production of the vesicles is by sonication of solution as described by Cable . In this method an aliquot of drug solution in buffer is added to the surfactant/cholesterol mixture in a 10-ml glass vial. The mixture is probe sonicated at 60°C for 3 minutes using a sonicator with a titanium probe to yield niosomes.

d.) Micro fluidization-

Micro fluidization is a recent technique used to prepare unilamellar vesicles of defined size distribution. This method is based on submerged jet principle in which two fluidized streams interact at ultra high velocities, in precisely defined micro channels within the interaction chamber. The impingement of thin liquid sheet along a common front is arranged such that the energy supplied to the system remains within the area of niosomes formation. The result is a greater uniformity, smaller size and better reproducibility of niosomes formed.

e.) Multiple membrane extrusion method-

Mixture of surfactant, cholesterol and dicetyl phosphate in chloroform is made into thin film by evaporation. The film is hydrated with aqueous drug polycarbonate membranes,
solution and the resultant suspension extruded through which are placed in series for upto 8 passages. It is a good method for controlling niosome size.

f.) Reverse Phase Evaporation Technique (REV)-

Cholesterol and surfactant (1:1) are dissolved in a mixture of ether and chloroform. An aqueous phase containing drug is added to this and the resulting two phases are sonicated at 4-5°C. The clear gel formed is further sonicated after the addition of a small amount of phosphate buffered saline (PBS). The organic phase is removed at 40°C under low pressure. The resulting viscous niosome suspension is diluted with PBS and heated on a water bath at 60°C for 10 min to yield niosomes.

Raja Naresh et al have reported the preparation of Diclofenac Sodium niosomes using Tween 85 by this method.

g.)Trans membrane pH gradient (inside acidic) Drug Uptake Process (remote Loading)-

Surfactant and cholesterol are dissolved in chloroform. The solvent is then evaporated under reduced pressure to get a thin film on the wall of the round bottom flask. The film is hydrated with 300 mM citric acid (pH 4.0) by vortex mixing. The multilamellar vesicles are frozen and thawed 3 times and later sonicated. To this niosomal suspension, aqueous solution containing 10 mg/ml of drug is added and vortexed. The pH of the sample is then raised to 7.0-7.2 with 1M disodium phosphate. This mixture is later heated at 60°C for 10 minutes to give niosomes.

h.) The "Bubble" Method-

It is novel technique for the one step preparation of liposomes and niosomes without the use of organic solvents. The bubbling unit consists of round-bottomed flask with three necks positioned in water bath to control the temperature. Water-cooled reflux and thermometer is positioned in the first and second neck and nitrogen supply through the third neck. Cholesterol and surfactant are dispersed together in this buffer (pH 7.4) at 70°C, the dispersion mixed for 15 seconds with high shear homogenizer and immediately afterwards "bubbled" at 70°C using nitrogen gas.

i.) Formation of niosomes from proniosomes-

Another method of producing niosomes is to coat a water-soluble carrier such as sorbitol with surfactant. The result of the coating process is a dry formulation. In which each water-soluble particle is covered with a thin film of dry surfactant. This preparation is termed "Proniosomes". The niosomes are recognized by the addition of aqueous phase at T > Tm and brief agitation.

T = Temperature.
Tm = mean phase transition temperature.

Blazek-Walsh A.I. et al have reported the formulation of niosomes from maltodextrin based proniosomes. This provides rapid reconstitution of niosomes with minimal residual carrier. Slurry of maltodextrin and surfactant was dried to form a free flowing powder, which could be rehydrated by addition of warm water.

Table 1: Drugs incorporated into niosomes by various methods-

Method of preparation	Drug incorporated
Ether Injection	Sodium stibogluconate Doxorubicin
Hand Shaking	Methotrexate Doxorubicin
Sonication	9-desglycinamide 8-arginine Vasopressin Oestradiol

4.2.Materials:-

a.) Surfactants-
The term surfactant is a blend of surface active agent. Surfactants are usuallyorganiccompounds that are amphiphilic, meaning they contain both hydrophobic groups (their tails) and hydrophilic groups (their heads). Therefore, a surfactant molecule contains both a water insoluble (and oil soluble component) and a water soluble component. Surfactant molecules will migrate to the water surface, where the insoluble hydrophobic group may extend out of the bulk water phase, either into the air or, if water is mixed with oil, into the oil phase, while the water soluble head group remains in the water phase. This alignment and aggregation of surfactant molecules at the surface, acts to alter the surface properties of water at the water/air or water/oil interface.
Nonionic sufactants:
Fatty alcohols:
eg.
Cetyl alcohol, Stearyl alcohol, Cetostearyl alcohol (consisting predominantly of cetyl and stearyl alcohols), Oleyl alcohol;
Polyoxyethylene glycol alkyl ethers (Brij): CH₃–(CH₂)_10–16–(O-C₂H₄)_1–25–OH:
eg.
Octaethylene glycol monododecyl ether, Pentaethylene glycol monododecyl ether;
Polyoxypropylene glycol alkyl ethers: CH₃–(CH₂)_10–16–(O-C₃H₆)_1–25–OH;
Glucoside alkyl ethers: CH₃–(CH₂)_10–16–(O-Glucoside)_1–3–OH: eg. Decyl glucoside, Lauryl glucoside, Octyl glucoside;

Polyoxyethylene glycol octylphenol ethers: C₈H₁₇–(C₆H₄)–(O-C₂H₄)_1–25–OH: eg.Triton X-100;
Polyoxyethylene glycol alkylphenol ethers:C₉H₁₉–(C₆H₄)–(O-C₂H₄)_1–25–OH: eg.Nonoxynol-9;
Glycerol alkyl esters: eg.Glyceryl laurate

Polyoxyethylene glycol sorbitan alkyl esters: eg.Polysorbates;

Sorbitan alkyl esters: eg.
Spans;

Block copolymers of polyethylene glycol and polypropylene glycol: eg.Poloxamers

b.) Cholesterol-
Steroids are important components of cell membranes and their presence in membranes brings about significant changes with regard to bilayer stability, fluidityand permeability. Cholesterol, a natural steroid, is the most commonly usedmembrane additive and can be incorporated to bilayers at high molar ratios. Cholesterol by itself, however, does not form bilayer vesicles. It is usuallyincluded in a 1:1 molar ratio in most formulations to prevent vesicle aggregationby the inclusion of molecules that stabilize the system against the formation ofaggregates by repulsive steric or electrostatic effects. It leads to the transition fromthe gel state to liquid phase in niosome systems. As a result, niosomes become lessleaky.
c.) Drug-
Entrapment of drug in niosomes increases vesicle size, probably by interaction of solute withsurfactant head groups, increasing the charge and mutual repulsion of the surfactant bilayers, thereby increasing vesicle size. In polyoxyethylene glycol (PEG) coated vesicles, some drug is entrapped in the long PEG chains, thus reducing the tendency to increase the size. The hydrophilic lipophilic balance of the drug affects degree of entrapment
d.) Other Additives-

As is the case with liposomes, charged phospholipids such as dicethylphosphate
(DCP) and stearyl amine (SA) have been used to produce charge in niosome formulations. The former molecule provides negative charge to vesicles whereas the later one is used in the preparation of positively charged (cationic) niosomes.

5.Evaluation parameters or Characterization of niosome:-

5.1.Separation of Unentrapped Drug:-

The removal of unentrapped solute from the vesicles can be accomplished by various techniques, which include: -

1. Dialysis-

The aqueous niosomal dispersion is dialyzed in dialysis tubing against phosphate buffer or normal saline or glucose solution.

2. Gel Filtration-

The unentrapped drug is removed by gel filtration of niosomal dispersion through a Sephadex-G-50 column and elution with phosphate buffered saline or normal saline.

3. Centrifugation-

The niosomal suspension is centrifuged and the supernatant is separated. The pellet is washed and then resuspended to obtain a niosomal suspension free from unentrapped drug
5.2.Evaluation parameters or Characterization of niosome-

a.) Size-
Shape of niosome vesicles assumed to be spherical, their mean diameter can be determined by using laser light scattering method . Also, diameter can be determined by using electron microscopy, molecular sieve chromatography, ultracentrifugation, photon correlation microscopy and optical microscopy

b.) Bilayer formation-
Assembly of non-ionic surfactants to form bilayer vesicle is characterized by X-cross formation under light polarization microscopy.

c.) Number of lamellae-
It is determined by using NMR spectroscopy, small angle X-ray scattering and electron microscopy

d.) Membrane rigidity-
Membrane rigidity can be measured by means of mobility of fluorescence probe as function of temperature

e.) Entrapment efficiency-

After preparing niosomal dispersion, unentrapped drug is separated by dialysis centrifugation, or gel filtration as described above and the drug remained entrapped in niosomes is determined by complete vesicle disruption using 50% n-propanol or 0.1% Triton X-100 and analysing the resultant solution by appropriate assay method for the drug. Where,

Percent (%) entrapped efficiency = [Entrapped drug (mg) / Total drug added (mg)] X 100

f.) Vesicle diameter-

Niosomes, similar to liposomes, assume spherical shape and so their diameter can be determined using light microscopy, photon correlation microscopy and freeze fracture electron microscopy. Freeze thawing (keeping vesicles suspension at –20°C for 24 hrs and then heating to ambient temperature) of niosomes increases the vesicle diameter, which might be attributed to fusion of vesicles during the cycle.

g.) In-vitro release-

A method of in-vitro release rate study includes the use of dialysis tubing. A dialysis sac is washed and soaked in distilled water. The vesicle suspension is pipetted into a bag made up of the tubing and sealed. The bag containing the vesicles is placed in 200 ml of buffer solution in a 250 ml beaker with constant shaking at 25°C or 37°C. At various time intervals, the buffer is analyzed for the drug content by an appropriate assay method.

h.) Stability of niosomes-

Vesicles are stabilized based upon formation of 4 different forces:

1. Van der Waals forces among surfactant molecules;
2. Repulsive forces emerging from the electrostatic interactions among charged groups of surfactant molecules;
3. Entropic repulsive forces of the head groups of surfactants;
4. short-acting repulsive forces.

Electrostatic repulsive forces are formed among vesicles upon addition of charged
Surfactants to the double layer, enhancing the stability of the system. Biological stability of the niosomes prepared with alkyl glycosides was investigated by Kiwada et al. They reported that niosomes were not stable enough in plasma. This may be due to single–chain alkyl surfactants. SUVs were found to be more stable. Niosomes in the form of liquid crystal and gel can remain stable at both room temperature and 4°C for 2 months. No significant difference has been observed between the stability of these two types of niosomes with respect to leakage. Even though no correlation between storage temperature and stability has been found, it is recommended that niosomes should be stored at 4°C. Ideally these systems should be stored dry for reconstitution by nursing staff or by the patient and when rehydrated should exhibit dispersion characteristics that are similar to the original dispersion. Simulation studies conducted to investigate physical stability of these niosomes during transportation to the end-user revealed that mechanical forces didn't have anyinfluence on physical stability. It is assumed that the reason behind the stability of niosomes may be due to the prevention of aggregation caused by steric interactions among large polar head groups of surfactants.

The factors which affect the stability of niosomes are as following:
• Type of surfactant;
• Nature of encapsulated drug;
• Storage temperature;
• Detergents;
• Use of membrane spanning lipids;
• The interfacial polymerization of surfactant monomers in situ;
• Inclusion of a charged molecule.

i.) Toxicity of niosomes-
Unfortunately, there is not enough research conducted to investigate toxicity of niosomes. Researchers measured proliferation of keratinocytes in one of the topical niosome formulations. The effect of surfactant type on toxicity was investigated. It was determined that the ester type surfactants are less toxic than ether type surfactants. This may be due to enzymatic degradation of ester bounds. In general, the physical form of niosomes did not influence their toxicity as evident in a study comparing the formulations prepared in the form of liquid crystals and gels. However, nasal applications of these formulations caused toxicity in the case of liquid crystal type niosomes. In some instances, encapsulation of the drug by niosomes reduces the toxicity as demonstrated in the study on preparation of niosomes containing vincristine. It decreased the neurological toxicity, diarrhoea and alopecia following the intravenous administration of vincristineand increased vincristine anti-tumor activity in S-180 sarcoma and Erlich ascites mouse models.

6.Applications-

Niosomal drug delivery is potentially applicable to many pharmacological agents for their action against various diseases. Some of their therapeutic applications are discussed below.

1) Targeting of bioactive agents-

a) To reticulo-endothelial system (RES)

The cells of RES preferentially take up the vesicles. The uptake of niosomes by the cells is also by circulating serum factors known as opsonins, which mark them for clearance. Such localized drug accumulation has, however, been exploited in treatment of animal tumors known to metastasize to the liver and spleen and in parasitic infestation of liver.

b) To organs other than RES

It has been suggested that carrier system can be directed to specific sites in the body by use of antibodies. Immunoglobulins seem to bind quite readily to the lipid surface, thus offering a convenient means for targeting of drug carrier. Many cells possess the intrinsic ability to recognize and bind particular carbohydrate determinants and this can be exploited to direct carriers system to particular cells.

2) Neoplasia-

Doxorubicin, the anthracyclic antibiotic with broad spectrum anti tumor activity, shows a dose dependant irreversible cardio toxic effect. Niosomal delivery of this drug to mice bearing S-180 tumor increased their life span and decreased the rate of proliferation of sarcoma. Niosomal entrapment increased the half-life of the drug, prolonged its circulation and altered its metabolism. Intravenous administration of methotrexate entrapped in niosomes to S-180 tumor bearing mice resulted in total regression of tumor and also higher plasma level and slower elimination.

3) Leishmaniasis-

Niosomes can be used for targeting of drug in the treatment of diseases in which the infecting organism resides in the organ of reticulo-endothelial system. Leishmaniasis is such a disease in which parasite invades cells of liver and spleen. The commonly prescribed drugs are antimonials, which are related to arsenic, and at high concentration they damage the heart, liver and kidney.

The study of antimony distribution in mice, performed by Hunter et al showed high liver level after intravenous administration of the carriers' forms of the drug.

Baillie et al reported increased sodium stibogluconate efficacy of niosomal formulation and that the effect of two doses given on successive days was additive.

4) Delivery of peptide drugs-

Yoshida et al investigated oral delivery of 9-desglycinamide, 8-arginine vasopressin entrapped in niosomes in an in-vitro intestinal loop model and reported that stability of peptide increased significantly.

5) Immunological application of niosomes-

Niosomes have been used for studying the nature of the immune response provoked by antigens. Brewer and Alexander have reported niosomes as potent adjuvant in terms of immunological selectivity, low toxicity and stability.

6) Niosomes as carriers for Hemoglobin-

Niosomes can be used as a carrier for hemoglobin. Niosomal suspension shows a visible spectrum superimposable onto that of free hemoglobin. Vesicles are permeable to oxygen and hemoglobin dissociation curve can be modified similarly to non-encapsulated hemoglobin.

7) Transdermal delivery of drugs by niosomes-

Slow penetration of drug through skin is the major drawback of transdermal route of delivery. An increase in the penetration rate has been achieved by transdermal delivery of drug incorporated in niosomes. Jayraman et al has studied the topical delivery of erythromycin from various formulations including niosomes or hairless mouse. From the studies, and confocal microscopy, it was seen that non-ionic vesicles could be formulated to target pilosebaceous glands.

8) Other Applications-

a) Sustained Release

Azmin et al suggested the role of liver as a depot for methotrexate after niosomes are taken up by the liver cells. Sustained release action of niosomes can be applied to drugs with low therapeutic index and low water solubility since those could be maintained in the circulation via niosomal encapsulation.

b) Localized Drug Action

Drug delivery through niosomes is one of the approaches to achieve localized drug action, since their size and low penetrability through epithelium and connective tissue keeps the drug localized at the site of administration.

Localized drug action results in enhancement of efficacy of potency of the drug and at the same time reduces its systemic toxic effects e.g. Antimonials encapsulated within niosomes are taken up by mononuclear cells resulting in localization of drug, increase in potency and hence decrease both in dose and toxicity.

The evolution of niosomal drug delivery technology is still at an infancy stage, but this type of drug delivery system has shown promise in cancer chemotherapy and anti-leishmanial therapy.

7. Marketed formulation of Niosome:-


	Brand:Estee Lauder - Estee Lauder - Beyond Paradise Name: Beyond Paradise After Shave Lotion 100ml/3.3oz Price:$39.00 Instr.:An active smoothing after-shave lotion ;Instantly soothes your skin after shaving ;Removes razor-burns & prolongs a clean shave ;Helps ensure & prolong, smooth skin result ;Suitable for all skin types ;
	Brand:White Shoulders - White Shoulders - Name: White Shoulders Eau De Cologne Spray 130ml/4.5oz Price:$38.00 Instr.:
	Brand:Orlane - Orlane - Lipcolor & Lipstick Name: Lip Gloss Price:$15.50 Instr.:Soft & gentle that glides on lips smoothly ;Instantly emphasizes your lips with shimmering effect ;Adds extra sparkle & shine ;Long lasing for hours ;Gives a sexy & sensual makeup effect ;
	Brand:Lancaster - Lancaster - Suractif - Night CareName: Suractif Non Stop Lifting Advanced Night Cream 50ml/1.7oz Price:$75.00 Instr.:Suractif Non Stop Lifting Advanced Night Cream ;
	Brand:Jean Paul Gaultier - Jean Paul Gaultier - Le Classique Name: Le Classique Eau De Toilette Spray 100ml/3.3oz Price:$79.00 Instr.:
	Brand:Nina Ricci - Nina Ricci - Love In Paris Name: Love In Paris Deodorant Spray 100ml/3.3oz Price:$31.50 Instr.:A strong & effective deodorant ;Provides long hour effective benefits ;Greatly helps regenerate perspiration ;Offers effective protection against odor & wetness ;Leaves skin feeling incredibly refreshed & clean ;Suitable for all skin types ;
	Brand:Liz Claiborne - Liz Claiborne - RealitiesName: Realities Shower Gel 200ml/6.7oz Price:$24.00 Instr.:
	Brand:Givenchy - Givenchy - Blanc Parfait - Day Care Name: Blanc Parfait W4-L Universal Brightening Spots Corrector SPF 45 1.6ml/0.05oz Price:$34.00 Instr.:Fine flesh-colored emulsion provides good coverage ;Immediately covers dark spots & unifies makeup ;Enriched with brightening ingredients ;Prevents appearance of dark spots ;Offers extremely high protection against harmful UV rays ;Skin regains its clarity & uniformity ;To use: Apply in morning after day cream onto needed areas ;
	Brand:Lancome - Lancome - Foundation & Complexion Name: Flash Retouche Brush On Concealer Price:$28.00 Instr.:Flash Retouche Brush On Concealer - No. 01 Voile de Lumiere ;
	Brand:Britney Spears - Britney Spears - CuriousName: Curious Coffret: Edp Spray 100ml+ Dual-ended Parfum & Pink Lipgloss+ Body Souffle 100ml 3pcs Price:$67.50 Instr.:
	Brand:Elene - Elene - Eye CareName: Day & Night Eye Programme 15mlx 2 Price:$69.50 Instr.:Two eye care products provided separately in one container ;Restores softness and elasticity to the skin ;Firms eye bags ;Reduces fine lines ;Prevents the appearance of dark circles ;
	Brand:Guinot - Guinot - Night CareName: Deep Action Whitening Serum 30ml/1.07oz Price:$52.50 Instr.:An intensive lightening serum ;Effectively fades out stubborn pigmentation ;Helps restore freshness & suppleness ;Illuminates healthy fair translucence ;Enhances an even-toned & unified appearance ;
	Brand:Gatineau - Gatineau - Moderactive - Cleanser Name: Moderactive Almond Make-Up Remover 250ml/8.3oz Price:$22.50 Instr.:A total almond makeup remover ;Removes & dissolves all makeup & impurities ;Helps eliminate makeup in seconds ;Provides optimal hydration while cleansing ;Leaves skin feeling completely clean & clear ;Suitable for all skin types ;
	Brand:Shiseido - Shiseido - Bio Performance - Night Care Name: Bio-Performance Intensive Clarifying Essence 40ml/1.3oz Price:$68.00 Instr.:With botanicals, vitamins & energizers Bio-EPO & HKC ;Increases the skin's ability to absorbs & retains moisture ;Improves smoothes & radiance ;
	Brand:Hugo Boss - Hugo Boss - Boss SoulName: Boss Soul After Shave 90ml/3oz Price:$46.00 Instr.:
	Brand:Givenchy - Givenchy - AmarigeName: Amarige Eau De Toilette Spray 100ml/3.3oz Price:$62.50 Instr.:A noble, pure & very unique fragrance ;Top notes are bright and sensual with neroli, mandarin and violet ;Middle notes are gardenia, and minosa, with ylang-ylang ;Finishes with ambergris, musk and vanilla ;Gives you the most freshest moments of the day ;Suitable for daily use ;
	Brand:Loris Azzaro - Loris Azzaro - ChromeName: Chrome Eau De Toilette Spray 200ml/6.8oz Price:$56.00 Instr.:
	Brand:Helena Rubinstein - Helena Rubinstein - HR - Golden Beauty - Body Care Name: Golden Beauty After Sun Soothing Moisturiser 150ml/5.07oz Price:$31.50 Instr.:A rich, creamy after sun care to neutralize the harmful effects of free radicals ;Strengthens skin natural defense mechanism to prevent signs of aging ;Quickly penetrates into skin & deeply nourishes skin ;Skin instantly feels fresh, calm & comfortable ;A smooth, luminous & longer lasting sun tan is developed ;Dermatologist tested ;
	Brand:Guinot - Guinot - CleanserName: Gentle Face Exfoliating Cream 50ml/1.7oz Price:$29.50 Instr.:Removes dead cells and impurities ;Smoothes and refines the skin textur ;Leaves skin soft and refreshed ;Suitable for all skin types ;

Figure: - lancomes

8. Recent development / future advancement:-

8.1. Anti glaucomatic niosomal system: recent trend in ocular drug delivery & research-
Glaucoma is adisease and characterized by an intraocular pressure higher than the eye can tolerate. The chronic glaucoma with open angle creates a major problem of public health and it is the second leading cause of blindness in the world. Because of the constraints of physiological factors such as lachrymal drainage, lower culdesacvolume, reflex tearing, drug spillage, and lower corneal permeability onto the cheek; the ocular bioavailability of conventional ophthalmic preparations is very poor. Conventional preparations require frequent instillation, and long term use of such preparations can cause ocular surface disorders. In recent years, significant efforts have been directed towards the development of new carrier systems for ocular drug delivery. Among these, non]ionic surfactant vesicles i.e. niosomes could be a potential one for the effective treatment of glaucoma patients and have gained popularity in ocular drug delivery research. This article reviews the constraints of conventional ocular therapy, complications of glaucoma therapy, and newer advances in the field of anti-glucomatic niosomal formulation.

The commonly used antiglaucomadrugs and their mechanism of action-
Drug/ MOA/ FDA approved medication-
a.
Prostaglandins (lanatoprost, travoprost)/ better outflow of fluids/ Lumigan (Allergan), Travatan (Alcon), Rescula (Novartis), Xalatan (Pfizer)

b.Beta blockers (timolol, betaxolol, levobunolol)/ decreasing fluid production/ Timoptic XE (Merck), Istalol (ISTA), Betoptic S (Alcon).

c.Topical
carbonic anhydrase inhibitors (dorzolamide, acetazolamide, brinzolamide) /decreasing rate of aqueous humor production /Trusopt (Merck), Azopt (Alcon)

d. á2 adrenoceptor agonist (brimonidine, apraclonidine)/ increasing uveoscleral outflow and decreasing aqueous production/ Iopidine (Alcon), Alphagan P (Allergan)

e.Epinephrine decreasing the rate of aqueous humor production and increasing the outflow Propine (Allergan)

8.2.Development of a topical niosomal preparation of acetazolamide: preparation and evaluation-
Orally administered acetazolamide has a limited use in glaucoma due to the systemic side effects associated with its use. No topical formulation of acetazolamide is available, mainly because of it having a limited aqueous solubility and poor corneal permeation. To enhance the bioavailability of acetazolamide by the topical route and to improve the corneal permeability of the drug, niosomes of acetazolamide were prepared (employing span 60 and cholesterol) by different methods. Transmission electron microscopy (TEM) of the selected formulation was carried out to study the morphology. Niosomes were also prepared in the presence of dicetyl phosphate and stearylamine to obtain negatively and positively charged vesicles, respectively. It was found that the reverse-phase evaporation method (REV) gave the maximum drug entrapment efficiency (43.75%) as compared with ether injection (39.62%) and film hydration (31.43%) techniques. Drug entrapment efficiency varied with the charge and the percent entrapment efficiency for the REV method was 43.75, 51.23 and 36.26% for neutral, positively charged and negatively charged niosomes, respectively. Corneal permeability studies, however, showed that the percent permeation and the apparent permeability coefficient for the charged niosomes were less than for the neutral ones. A bioadhesive niosomal formulation of acetazolamide was also prepared and compared with the positively charged formulation, considering that both of them would have a prolonged stay in the cul-de-sac because of their expected interactions with mucin. The formulations were also compared based on their intraocular pressure (IOP)-lowering capacity. The positively charged niosomes (REV2), although showing good corneal permeability and pharmacodynamics, were however found to be inappropriate in terms of the corneal cell toxicity. The bioadhesive coated formulation (REV1bio) compared well with REV2 and also showed a much lesser toxicity. Further, the IOP-lowering effect of the developed formulations was compared with that of a marketed formulation of dorzolamide 2%, a topical carbonic anhydrase inhibitor. The developed niosomal formulations of acetazolamide showed a comparable physiological effect (33% reduction of IOP in REV***1bio and 37% reduction in dorzolamide) with a duration of up to 6 h (the duration being 3 h for dorzolamide). Results of the study indicate that it is possible to develop a safe (as indicated by corneal toxicity studies) and physiologically active topical niosomal formulation of acetazolamide relative in efficiency to the newer local carbonic anhydrase inhibitor, dorzolamide. The developed formulations can form a cost effective treatment plan, which is especially important in the treatment of glaucoma, a chronic ailment affecting middle-aged to old patients.
8.3. Advances in novel parentral drug delivery systems-
The parenteral administration route is the most effective and common form of delivery for active drug substances with poor bioavailability and the drugs with a narrow therapeutic index. Drug delivery technology that can reduce the total number of injection throughout the drug therapy period will be truly advantageous not only in terms of compliance, but also to improve the quality of the therapy. Such reduction in frequency of drug dosing is achieved by the use of specific formulation technologies that guarantee the release of the active drug substance in a slow and predictable manner. The development of new injectable drug delivery system has received considerable attention over the past few years. A number of technological advances have been made in the area of parenteral drug delivery leading to the development of sophisticated systems that allow drug targeting and the sustained or controlled release of parenteral medicines

9. References:-

1. Theresa M.A., Drugs published by Adis international Ltd., 1998; 56(5):747-756.

2. Breimer D.D. and Speiser R. Topics in pharmaceutical Sciences. 5 Elsevier Science Publishers, New York, USA. 1985; p.291.

3. Malhotra M. and Jain N.K. Niosomes as Drug Carriers. Indian Drugs (1994), 31 (3): 81-86.

4. Malhotra M. and Jain N.K. Niosomes as Drug Carriers. Indian Drugs (1994), 31 (3): 81-86.
5. Buckton G., Harwood, Interfacial phenomena in Drug Delivery and Targeting Academic Publishers, Switzerland. 1995; p.154-155.
6. Don A., Van H., Joke A.B. and Hans E. Non ionic surfactant vesicles containing estradiol for topical application. Ph.D. thesis. Centre for drug research. 1997; p. 330-339.
7. Handjani-Vila R.M., Ribier A., Rondot B. and Vanlerberghe G. Dispersions of lamellar phases of non-ionic lipids in cosmetic products. Int. J. Cosmetic Sci. 1979; 1:303–314.
8. Azmin M.N., Florence A.T., Handjani-Vila R.M., Stuart J.F.B., Vanlerberghe G., and Whittaker J.S. The effect of non-ionic surfactant vesicle (niosome) entrapment on the absorption and distribution of methotrexate in mice. J. Pharm. Pharmacol. 1985; 37: 237–242.
9. Sheena I.P., Singh U.V., Kamath R., Uma Devi P., and Udupa N. Niosomal withaferin A, with better tumor efficiency. Indian J. Pharm. Sci. 1998; 60(1):45-48.
10. McCormack B. and Gregordias G., Drugs-in-cyclodextrins-in-liposomes: an approach to controlling the fate of water insoluble drugs in vivo. Int. J. Pharm. 1998; 162: 59-69
11.Vincent Baeyens, Christine Percicot, Monia Zignani, Arati A. Deshpande, Vassilios Kaltsatos, Robert Gurn. Ocular drug delivery in veterinary medicine, Adv. Drug Deliv. Rev. 1997, 28, 335–361,
12. Harisha Atluri, Banmeet S. Anand, Jignesh Patel, Ashim K. Mitra, Mechanism of a model dipeptide transport across blood-ocular barriers following systemic administration, Exp. Eye. Res. 2004, 78, 815–822.
13. Pranav sharma, Kamal dua, Sharma VK, Sara U.V.S, Yadav V.P, Samad A, Sunil Prajapati, Ophathalmic drug delivery system, The Indian Pharmacist 2008, VII, 76.
14. Aggarwal D, and Kaur IP. Improved pharmacodynamics of timolol maleate from a mucoadhesive niosomal opthalmic drug delivery system. Int.J. Pharm. 290: 155 (2005).

15. Almira I. Blazek-welsh I A and Rhodes G D. Maltodextrin – Based proniosomes.AAPS PharmSciTech. 3: 36. (2001).

16.Alsarra AI, Bosela AA, Ahmed MS, and Mahrous M G.Proniosomes as a drug carrier for Arunothayanum P. et al.Investigation into the in vitro/in vivo behaviour of polyhedral niosomes. J. Pharm.Pharmcol. 50(supp): l169 (1998).

17. Baillie AJ. The preparation and properties of niosomes-nonionic surfactant vesicles. J.Pharm. Pharmacol. 37: 863 (1985).

Herb–drug interactions: an overview of the clinical evidence

2010-11-16T00:49:00.000-08:00

Herb–drug interactions: an overview of the

clinical evidence

ABSTRACT

Herbal medicines are mixtures of more than one active ingredient. The multitude of pharmacologically active compounds obviously increases the likelihood of interactions taking place. Hence, the likelihood of herb–drug interactions is theoretically higher than drug–drug interactions, if only because synthetic drugs usually contain single chemical entities. Case reports and clinical studies have highlighted the existence of a number of clinically important interactions, although cause-and-effect relationships have not always been established. Herbs and drugs may interact either pharmacokinetically or pharmacodynamically. Through induction of Cytochrome P-450 enzymes and/or P-glycoprotein, some herbal products (e.g. St John’s wort) have been shown to lower the plasma concentration (and/or the pharmacological effect) of a number of conventional drugs, including cyclosporine, indinavir, irinotecan, nevirapine, oral contraceptives and digoxin. The majority of such interactions involve medicines that require regular monitoring of blood levels. To date there is less evidence relating to the pharmacodynamic interaction. However, for many of the interactions discussed here, the understanding of the mechanisms involved is incomplete. Taking herbal agents may represent a potential risk to patients under conventional pharmacotherapy.

KEY words

Herbal drugs, drug–drug interactions, Cytochrome P-450, oral contraceptives, indinavir,

INTRODUCTION

Due to the growing use of herbals and other dietary supplements healthcare providers and consumers need to know whether problems might arise from using these preparations in combination with conventional drugs. The use of herbal products has dramatically increased over the past decade, driving physicians to become educated in regards to potential herbal complications and drug interactions. From 1990 to 1997, the herbal product market increased by 48%, with 42% of the population using alternative treatments and spending an estimated $27 billion on them [1] Herbal products are widely available, relatively inexpensive, and often make alluring but unsubstantiated claims. Herbal medicine appeals to consumers who believe that natural herbal products are preferable to synthetic pharmaceuticals [2]. A relevant safety concern associated to the use of herbal medicines is the risk of interaction with prescription medications [3-7]. This issue is especially important with respect to drugs with narrow therapeutic indexes, such as warfarin or digoxin [8]. Recent examinations have indicated that as many as16% of prescription drug users consume herbal supplements . Exacerbating the problem, herbal remedies are often marketed on the Internet with misleading and unproved claims.

Despite repeated warnings, consumers continue to equate ‘‘natural’’ with safe. As use becomes more prevalent and reports of adverse effects continue mount, there is an increasing need for health care professionals to understand better the potential complications associated with these herbal remedies. There are numerous products currently on the market that have been associated with toxicity. The aim of this article is to highlight the clinical interactions between herbal remedies and prescribed drugs. Theoretical herb drug interactions, which are based on in vitro experiments, animal studies, speculative and/or empirical evidence can be found elsewhere[9].

The nature of herbal–drug interactions

Natural products, unlike conventional drugs, provide a complex mixture of bioactive entities, which may or may not provide therapeutic activity. Often a complete characterization of all the chemical constituents from a natural product is unknown.

Additionally, chemical makeup of a natural product may vary depending on the part of the plant processed (stems, leaves, roots), seasonality and growing conditions. Combination products composed of multiple natural products complicate matters further. Not only does the complex nature of natural products complicate the determination of drug–herbal interactions, but the manufacturing process contributes to the overall complexity as well. Because herbal products are not regulated by the FDA, as previously stated, there are no standards for herbal products. Indeed, some products have been found to be misidentified, substituted and/or adulterated with other natural products or unwanted substances. Testing of the quality of more than 1200 dietary supplement products by the independent laboratory ConsumerLab.com found that 1 in 4 dietary supplement products lacked the labeled ingredients or had other serious problems such as unlisted ingredients or contaminants. This creates a problem when evaluating the validity of drug–herbal interactions [10].

MECHANISMS OF HERB–DRUG INTERACTIONS

Herbal medicines follow modern pharmacological principles. Hence, herb–drug interactions are based on the same pharmacokinetic and pharmacodynamic mechanisms as drug–drug interactions [11]. Pharmacokinetic interactions have been more extensively studied and in vitro and in vivo studies indicated that the altered drug concentrations by co-administered herbs may be attributable to the induction (or inhibition) of hepatic and intestinal drug-metabolizing enzymes [particularly Cytochrome P-450 (CYP)], and/or drug transporters such as P-glycoprotein [12-13]. The CYP is the most important phase I drug-metabolizing enzyme system, responsible for the metabolism of a variety of drugs. Many herbs (e.g. St John’s wort, echinacea, kava and garlic) and natural compounds isolated from herbs (e.g. flavonoids, coumarins, furanocoumarins, anthraquinones, caffeine and terpenes) have been identified as substrates, inhibitors and/or inducers of various CYP enzymes [14]. Specifically, clinical studies have shown that long-term (2 weeks) St John’s wort administration significantly induced intestinal and hepatic CYP3A4 and possibly other CYP enzymes involved in drugs metabolism [15-21]. Moreover, a clinical study performed on 12 healthy subjects showed that echinacea modulated the catalytic activity of CYP3A at hepatic and intestinal sites (induction of hepatic CYP3A4 and inhibition of intestinal CYP3A4). By contrast, a number of herbal medicines, including green tea ginkgo garlic saw palmetto and Siberian ginseng [22] did not affect CYP3A4 and CYP2D6 activities in normal volunteers. P-glycoprotein in the intestine, liver and kidney may play an important role in the absorption, distribution, or excretion of drugs. P-glycoprotein appears to limit the cellular transport from intestinal lumen into epithelial cells and also enhances the excretion of drugs out of hepatocytes and renal tubules into the adjacent luminal space [23]. Like CYP, P-glycoprotein is vulnerable to inhibition, activation, or induction by herbs and herbal constituents. Curcumin, ginsenosides, piperine, sylimarin and catechins may affect P-glycoprotein-mediated drug transport [24]. St John’s wort induces the intestinal expression of P-glycoprotein both in isolated cells and in healthy volunteers. Hyperforin, a major ingredient of St John’s wort, binds to orphan pregnane X receptor resulting in a series of intracellular events leading to the expression of CYP3A4 and P-glycoprotein. A few pharmacodynamic interactions have also been described. Pharmacodynamic interactions may be additive (or synergetic), whereby the herbal medicine potentiates the action of synthetic drugs (e.g. interaction between the anticoagulant warfarin with antiplatelet herbs), or antagonistic, whereby the herbal medicine reduces the efficacy of synthetic drugs (e.g. kava possesses dopaminergic antagonistic properties and hence might reduce the pharmacological activity of the anti-parkinson drug levodopa) [25].

LIMITATIONS

Much of the available information about the interaction between herbal products and prescribed drugs is gleaned from case reports, although clinical studies are now also beginning to appear in the literature. The published case reports are often incomplete as they do not allow us to conclude that a causal relationship exists. Even documented case reports have to be interpreted with great caution, as causality is not usually established beyond reasonable doubt. According to the scoring system described by Fugh-Berman and Ernst [26], 68.5% of the cases reported were classified as ‘unevaluable’ (i.e. reports contained inadequate information to assess the likelihood of an interaction), 18.5% were classified as ‘possible’ (i.e. reports provided some evidence for an interaction, but there may be other causes of the event) and 13% as ‘well documented’ (reports appeared to provide reliable evidence for an interaction.

Herbal medicine involved in Drug interaction

Drug	Herb	Result of interaction	Possible mechanism	Source of evidence	Referene
Digoxin	Gum guar, St John’s wort, wheat bran	Decreased plasma digoxin concentration	Multiple mechanisms: (i) gum guar delays gastric emptying and hence may reduce digoxin absorption (ii) St John’s wort induces P-glycoprotein which is involved in digoxin absorption/ excretion (iii) Fibres in bran may trap digoxin in the gut.	Clinical studies	27-30
Aspirin	Ginkgo	Spontaneous hyphema	Additive effect on platelet aggregation (ginkgolides have antiplatelet activity)	A case report	31
Lovastatin	Pectin or oat bran	Decreased absorption of lovastatin	Pectins or bran fibres may bind or trap lovastatin in the gut.	A clinical study	32
Simvastatin	St John’s wort	Decreased plasma digoxin concentration	Simvastatin is a substrate of P-glycoprotein and is metabolized by CYP enzymes. Both CYP enzymes and P-glycoprotein are induced by St John’s wort	A clinical study	33
Phenprocoumon	Ginger St John’s wort	(i) Over-anticoagulation (ii) decreased anticoagulant effect	(i) Additive effect on coagulation (ginger inhibits platelet aggregation) (ii)Phenprocoum n is metabolised by cytochrome enzymes which are induced by St John’s wort.	A case report A clinical study	34 35
Verapamil	St John’s wort	Decreased bioavailability of verapamil	Induction of intestinal CYP3A4 by St John’s wort.	A clinical study	36
Alprazolam Amitriptyline Buspironea	St John’s wort St John’s wort St John’s wort	Decreased plasma levels of alprazolam Decreased plasma levels of amitriptyline Hypomania	Alprazolam is a specific probe for CYP 3A4, which is induced by St John’s wort. Amitriptyline is a substrate of both CYP2C19 and P-glycoprotein which are induced by St John’s wort. Synergistic effect on 5-HT receptors	Clinical studies A clinical study A case report	37-38 39 40

Conclusion

Based on current evidence from in vitro, in vivo and clinical studies, herbals and other dietary supplements interact with many drugs. Still, drug-herbal interactions are difficult to evaluate because of the lack of reliability of these products. The interactions often involve drug-metabolizing enzymes and drug transporter systems, although pharmacodynamic interactions can also be involved. Because the pharmacokinetic and pharmacodynamic characteristics of most herbal and other dietary supplements are not completely recognized, potential interactions are not often predictable. Potential interactions are more likely to occur with drugs with narrow therapeutic indexes. The evidence-based evaluation used in the study can be used to evaluate the reliability of case reports.

REFERENCE:

Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. JAMA 1998; 280: 1569–75.
Kaptchuk TJ, Eisenberg DM. The persuasive appeal of alternative medicine. Ann Intern Med 1998;129:1061–5.
Izzo A.A., Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs (2001) 61 2163–2175.
Brazier N.C., Levine M.A. Drug-herb interaction among commonly used conventional medicines: a compendium for health care professionals. Am. J. Ther. (2003) 10 163–169.
Fugh-Berman A., Ernst E. Herb-drug interactions: review and assessment of report reliability. Br. J. Clin. Pharmacol. (2001) 52 587–595.
Markowitz J.S., DeVane C.L. The emerging recognition of herb-drug interactions with a focus on St. John’s wort (Hypericum perforatum). Psychopharmacol. Bull. (2001) 35, 53–64.
Williamson E.M. Drug interactions between herbal and prescription medicines. Drug Saf. (2003) 26 1075–1092.
Izzo A.A. Drug interactions with St. John’s wort (Hypericum perforatum): a review of the clinical evidence. Int. J. Clin. Pharmacol. Ther. (2004) 42 139–148.
Ernst E. Possible interactions between synthetic and herbal medicinal products. Part 1: a systematic review of the indirect evidence. Perfusion (2000) 13 2200–2211.
Anon, 2005b. ConsumerLab.com's guide to buying vitamins and minerals. ConsumerLab.com. http://consumerslab.com/book/index.asp. Accessed February 17, 2005.
Izzo A.A., Borrelli F., Capasso R. Herbal medicine: the dangers of drug interaction. Trends Pharmacol. Sci. (2002) 23 358–359.
Zhou S., Gao Y., Jiang W., Huang M., Xu A., Paxton J.W. Interactions of herbs with cytochrome P450. Drug Metab. Rev. (2003) 35 35–98

Ioannides C. Pharmacokinetic interactions between herbal remedies and medicinal drugs. Xenobiotica (2002) 32 451–478.
Roby C.A., Anderson G.D., Kantor E., Dryer D.A., Burstein A.H. St John’s wort: effect on CYP3A4 activity. Clin. Pharmacol. Ther. (2000) 67 451–457.
Wang Z., Gorski J.C., Hamman M.A., Huang S.M., Lesko L.J., Hall S.D. The effects of St John’s wort (Hypericum perforatum) on human cytochrome P450 activity. Clin. Pharmacol. Ther. (2001) 70 317–326.
Bauer S., Stormer E., Johne A. et al. Alterations in cyclosporine A pharmacokinetics and metabolism during treatment with St John’s wort in renal transplant patients. Br. J. Clin. Pharmacol. (2003) 55 203–211.
Hall S.D., Wang Z., Huang S.M. et al. The interaction between St John’s wort and an oral contraceptive. Clin. Pharmacol. Ther. (2003) 74 525–535.
Markowitz J.S., Donovan J.L., DeVane C.L. et al. Effect of St John’s wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA (2003) 290 1500–1504.
Di Carlo G., Borrelli F., Ernst E., Izzo A.A. St John’s wort: Prozac from the plant kingdom. Trends Pharmacol. Sci. (2001) 22 292–297.
Markowitz J.S., Donovan J.L., DeVane C.L. et al. Effect of St. John’s wort on drug metabolism by induction of cytochrome P-450 3A4 enzyme. Obstet. Gynecol. Surv. (2004) 59 358– 359.
Donovan J.L., DeVane C.L., Chavin K.D., Taylor R.M., Markowitz J.S. Siberian ginseng (Eleutheroccus senticosus) effects on CYP2D6 and CYP3A4 activity in normal volunteers. Drug Metab. Dispos. (2003) 31 519–522.
Lin J.H., Yamazaki M. Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin. Pharmacokinet. (2003) 59-98

Zhou S., Lim L.Y., Chowbay B. Herbal modulation of P-glycoprotein. Drug Metab. Rev. (2004) 36 57–104.
Izzo A.A., Borrelli F., Capasso R. Herbal medicine: the dangers of drug interaction. Trends Pharmacol. Sci. (2002) 23 358–359.
Fugh-Berman A., Ernst E. Herb-drug interactions: review and assessment of report reliability. Br. J. Clin. Pharmacol. (2001), 52 587–595.
Johne A., Brockmoller J., Bauer S., Maurer A., Langheinrich M., Roots I. Pharmacokinetic interaction of digoxin with an herbal extract from St John’s wort (Hypericum perforatum). Clin. Pharmacol. Ther. (1999) 66 338–345.
Mueller S.C., Uehleke B., Woehling H. et al. Effect of St John’s wort dose and preparations on the pharmacokinetics of digoxin. Clin. Pharmacol. Ther. (2004) 75 546–557.
Huupponen R., Seppala P., Iisalo E. Effect of guar gum, a fibre preparation, on digoxin absorption in man. Eur. J. Clin. Pharmacol. (1984) 26 279–281.
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Matthews M.K., Jr. Association of Ginkgo biloba with intracerebral hemorrhage. Neurology (1998) 50 1933–1934.
Richter W.O., Jacob B.G., Schwandt P. Interaction between fibre and lovastatin. Lancet (1999) 338 706.
Sugimoto K., Ohmori M., Tsuruoka S. et al. Different effects of St John’s wort on the pharmacokinetics of simvastatin and pravastatin. Clin. Pharmacol. Ther. (2001) 70 518–524.
Kruth P., Brosi E., Fux R., Morike K., Gleiter C.H. Ginger associated overanticoagulation by phenprocoumon. Ann. Pharmacother. (2004) 38 257–260.
Yue Q.Y., Jansson K. Herbal drug and anticoagulant effect with and without warfarin: possibly related to the vitamin E component. J. Am. Geriatr. Soc. (2001) 49 838.
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Tam L.S., Chan T.Y., Leung W.K., Critchley J.A. Warfarin interactions with Chinese traditional medicines: danshen and methyl salicylate medicated oil. Aust. N. Z. J. Med. (1995) 225-238.
Jiang X., Williams K.M., Liauw W.S. et al. Effect of St John’s wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br. J. Clin. Pharmacol. (2004) 57 592–599.
A., Schmider J., Brockmoller J. et al. Decreased plasma levels of amitriptyline and its metabolites on comedication with an extract from St. John’s wort (Hypericum perforatum). J. Clin. Psychopharmacol. (2002) 22 46–54.
Dannawi M. Possible serotonin syndrome after combination of buspirone and St John’s wort. J. Psychopharmacol. (2002) 16

41 Gorski J.C., Huang S.M., Pinto A. et al. The effect of Echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo. Clin. Pharmacol. Ther. (2004) 89–100.

42 Schelosky L., Raffauf C., Jendroska K., Poewe W. Kava and dopamine antagonism. J. Neurol. Neurosurg. Psychiatry (1995) 58 639–640.

43 Shader R.I., Greenblatt D.J. Phenelzine and the dream machine – ramblings and reflections. J. Clin. Psychopharmacol. (1985) 5 65.

44 Dandekar U.P., Chandra R.S., Dalvi S.S. et al. Analysis of a clinically important interaction between phenytoin and Shankhapushpi, an Ayurvedic preparation. J. Ethnopharmacol. (1992) 35 285–288.

45 Shaw D., Leon C., Kolev S., Murray V. Traditional remedies and food supplements. A 5-year toxicological study (1991– 1995). Drug Saf. (1997) 17 342–356.

pharma job cover letter new

2010-11-15T02:11:00.001-08:00

Your name

Your Address

Your City state, zip

Your Phone number,

Your Email

Date

Name

Position,

Department

Office address,

City, State, Zip.

Dear Sir,

This is in reference to the pharmacy job advertised in the (name of the newspaper) dated (provide the date).

I am a pharmacy graduate from ( university name ) and has done my post graduation from ( university name).I am currently working in( name of the company ) and is interested to move to your company as I have read that you work on the modern technology.

I feel that the job at your company is more challenging and I can secure more experience and knowledge working at (company name).I had always dreamt of working in leading pharmaceutical company like yours where I can get trainees in the modern medical sciences and grow professionally.

I am sure that the exposure and skills that I have gained from the current company will help me work in your office. As I am sure my qualifications and experience will match with your requirements and assure you that with my dedication and hard work we can get mutual benefits.

I have enclosed my resume for your review and I am looking forward to attend an interview and discuss further interest in joining your company.

Thanking you ,

Sincerely,

Your Name.

sample cover letter for pharma jobs

2010-11-15T02:09:00.000-08:00

Pharma jobs are no longer an easy to reach thing. In fact it’s a daunting task to get the right job that you are looking for. So when you are applying for a pharma job make sure that your cover letter must be expressive enough. Highlight your area of interest and expertise, explain about your education and experience and relates it with the post you are applying for. Make the reader feels as only you are the right candidate for it.

Here is a sample pharma job cover letter:

From:

Ajay Prakash

S-10, LifeAround Avenue,

New Colony,

Colombia

To:

Mr. Roderick Tipton

Sprit Pharmaceuticals,

Trade Road,

Colombia

15th June, 2010

Dear Mr. Dubey,

This letter is in response to your advertisement of an opening in pharmacy research division posted on your company website. I found that my skills and experience match this position, so I would like to offer my services for this post.

I hold a professional degree in clinical pharmacy and have five years of work experience in the same field. Experimenting with biochemical compounds and discovering new medicines was my day to day work. Along with the following of set protocol, I made few new test methods which were very effective in diagnosis of the biochemical reactions that took place during the experiments.

I strongly believe that with the rapidly changing environment, need of good and authentic pharmacy research is in demand to produce immune friendly drugs. I can assure you that I will be an asset to your team and will bring the right and appropriate production in process.

I would appreciate the opportunity to have a personal meeting with you and looking for a call for the same.

Thank You,

Sincerely

Ajay Prakash

(241-877-6600)

High performance liquid chromatography

2010-11-14T02:22:00.001-08:00

High performance liquid chromatography
high performance liquid chromatography
.

High-performance liquid chromatography (or High pressure liquid chromatography, HPLC) is a form of column chromatography used frequently in biochemistry and analytical chemistry to separate, identify, and quantify compounds. HPLC utilizes a column that holds chromatographic packing material (stationary phase), a pump that moves the mobile phase(s) through the column, and a detector that shows the retention times of the molecules. Retention time varies depending on the interactions between the stationary phase, the molecules being analyzed, and the solvent(s) used.
Operation
•
the sample to be analyzed is introduced in small volume to the stream of mobile phase and is retarded by specific chemical or physical interactions with the stationary phase as it traverses the length of the column. The amount of retardation depends on the nature of the analyte, stationary phase and mobile phase composition. The time at which a specific analyte elutes (comes out of the end of the column) is called the retention time and is considered a reasonably unique identifying characteristic of a given analyte. The use of pressure increases the linear velocity (speed) giving the components less time to diffuse within the column, leading to improved resolution in the resulting chromatogram. Common solvents used include any miscible combinations of water or various organic liquids (the most common are methanol and acetonitrile). Water may contain buffers or salts to assist in the separation of the analyte components, or compounds such as trifluoroacetic acid which acts as an ion pairing agent.
A further refinement to HPLC has been to vary the mobile phase composition during the analysis; this is known as gradient elution. A normal gradient for reversed phase chromatography might start at 5% methanol and progress linearly to 50% methanol over 25 minutes, depending on how hydrophobic the analyte is. The gradient separates the analyte mixtures as a function of the affinity of the analyte for the current mobile phase composition relative to the stationary phase. This partitioning process is similar to that which occurs during a liquid-liquid extraction but is continuous, not step-wise. In this example, using a water/methanol gradient, the more hydrophobic components will elute (come off the column) under conditions of relatively high methanol (which is hydrophobic); whereas the more hydrophilic compounds will elute under conditions of relatively low methanol/high water. The choice of solvents, additives and gradient depend on the nature of the stationary phase and the analyte. Often a series of tests are performed on the analyte and a number of generic runs may be processed in order to find the HPLC method which gives the best separation of peaks.
Types of HPLC
Normal phase chromatography
Also known Normal phase HPLC (NP-HPLC), this method separates analytes based on polarity; it was the first kind of HPLC that chemists developed. NP-HPLC uses a polar stationary phase and a non-polar mobile phase, and works effectively for relatively polar analytes. The polar analyte associates with and is retained by the polar stationary phase. Adsorption strengths increase with increased analyte polarity, and the interaction between the polar analyte and the polar stationary phase (relative to the mobile phase) increases the elution time. The interaction strength depends not only on the functional groups in the analyte molecule, but also on steric factors. The effect of sterics on interaction strength allows this method to resolve (separate) structural isomers.
Use of more polar solvents in the mobile phase will decrease the retention time of the analytes, wheras more hydrophobic solvents tend to increase retention times. Very polar solvents in a mixture tend to deactivate the column by occupying the stationary phase surface. This is somewhat particular to normal phase because it is most purely an adsorptive mechanism (the interactions are with a hard surface rather than a soft layer on a surface).
NP-HPLC had fallen out of favor in the 1970s with the development of reversed-phase HPLC because of a lack of reproducibility of retention times as water or protic organic solvents changed the hydration state of the silica or alumina chromatographic media. Recently it has become useful again with the development of HILIC bonded phases which improve reproducibility.
Reversed phase chromatography
Reversed phase HPLC (RP-HPLC or RPC) has a non-polar stationary phase and an aqueous, moderately polar mobile phase. One common stationary phase is a silica which has been treated with RMe2SiCl, where R is a straight chain alkyl group such as C18H37 or C8H17. With these stationary phases, retention time is longer for molecules which are more non-polar, while polar molecules elute more readily. An investigator can also increase retention time by adding a polar solvent to the mobile phase, or decrease retention time by adding a more hydrophobic solvent. RPC is so commonly used that it is often incorrectly referred to as "HPLC" without further specification. The pharmaceutical industry regularly employs RPC to qualify drugs before their release.
RPC operates on the principle of hydrophobic interactions, which result from repulsive forces between a polar eluent, the relatively non-polar analyte, and the non-polar stationary phase. The binding of the analyte to the stationary phase is proportional to the contact surface area around the non-polar segment of the analyte molecule upon association with the ligand in the aqueous eluent. This solvophobic effect is dominated by the force of water for "cavity-reduction" around the analyte and the C18-chain versus the complex of both. The energy released in this process is proportional to the surface tension of the eluent (water: 7.3 × 10-6 J/cm², methanol: 2.2 × 10-6 J/cm²) and to the hydrophobic surface of the analyte and the ligand respectively. The retention can be decreased by adding a less polar solvent (methanol, acetonitrile) into the mobile phase to reduce the surface tension of water. Gradient elution uses this effect by automatically changing the polarity of the mobile phase during the course of the analysis.
Structural properties of the analyte molecule play an important role in its retention characteristics. In general, an analyte with a larger hydrophobic surface area (C-H, C-C, and generally non-polar atomic bonds, such as S-S and others) results in a longer retention time because it increases the molecule's non-polar surface area, which is non-interacting with the water structure. On the other hand, polar groups, such as -OH, -NH2, COO- or -NH3+ reduce retention as they are well integrated into water. Very large molecules, however, can result in an incomplete interaction between the large analyte surface and the ligand's alkyl chains and can have problems entering the pores of the stationary phase.
Retention time increases with hydrophobic (non-polar) surface area. Branched chain compounds elute more rapidly than their corresponding linear isomers because the overall surface area is decreased. Similarly organic compounds with single C-C-bonds elute later than those with a C=C or C-C-triple bond, as the double or triple bond is shorter than a single C-C-bond.
Aside from mobile phase surface tension (organizational strength in eluent structure), other mobile phase modifiers can affect analyte retention. For example, the addition of inorganic salts causes a moderate linear increase in the surface tension of aqueous solutions (ca. 1.5 × 10-7 J/cm² per Mol for NaCl, 2.5 × 10-7 J/cm² per Mol for (NH4)2SO4), and because the entropy of the analyte-solvent interface is controlled by surface tension, the addition of salts tend to increase the retention time. This technique is used for mild separation and recovery of proteins and protection of their biological activity in protein analysis (hydrophobic interaction chromatography, HIC).
Another important component is the influence of the pH since this can change the hydrophobicity of the analyte. For this reason most methods use a buffering agent, such as sodium phosphate, to control the pH. The buffers serve multiple purposes: they control pH, neutralize the charge on any residual exposed silica on the stationary phase and act as ion pairing agents to neutralize charge on the analyte. Ammonium formate is commonly added in mass spectrometry to improve detection of cerain analytes by the formation of ammonium adducts. A volatile organic acid such as acetic acid, or most commonly formic acid, is often added to the mobile phase if mass spectrometry is used to analyze the column eluent. Trifluoroacetic acid is used infrequently in mass spectrometry applications due to its persistence in the detector and solvent delivery system, but can be effective in improving retention of analytes such as carboxylic acids in applications utilizing other detectors, as it is one of the strongest organic acids. The effects of acids and buffers vary by application but generally improve the chromatography.
Reversed phase columns are quite difficult to damage compared with normal silica columns; however, many reversed phase columns consist of alkyl derivatized silica particles and should never be used with aqueous bases as these will destroy the underlying silica particle. They can be used with aqueous acid, but the column should not be exposed to the acid for too long, as it can corrode the metal parts of the HPLC equipment. RP-HPLC columns should be flushed with clean solvent after use to remove residual acids or buffers, and stored in an appropriate composition of solvent. The metal content of HPLC columns must be kept low if the best possible ability to separate substances is to be retained. A good test for the metal content of a column is to inject a sample which is a mixture of 2,2'- and 4,4'- bipyridine. Because the 2,2'-bipy can chelate the metal, the shape of the peak for the 2,2'-bipy will be distorted (tailed) when metal ions are present on the surface of the silica.[citation needed]..
Size exclusion chromatography
Size exclusion chromatography (SEC), also known as gel permeation chromatography or gel filtration chromatography, separates particles on the basis of size. It is generally a low resolution chromatography and thus it is often reserved for the final, "polishing" step of a purification. It is also useful for determining the tertiary structure and quaternary structure of purified proteins.
This technique is widely used for the molecular weight determination of polysaccharides. SEC is the official technique (suggested by European pharmacopeia) for the molecular weight comparison of different commercially available low-molecular weight heparins.
Ion exchange chromatography.
In ion-exchange chromatography, retention is based on the attraction between solute ions and charged sites bound to the stationary phase. Ions of the same charge are excluded. Types of ion exchangers include:
• Polystyrene resins – These allow cross linkage which increases the stability of the chain. Higher cross linkage reduces swerving, which increases the equilibration time and ultimately improves selectivity.
• Cellulose and dextran ion exchangers (gels) – These possess larger pore sizes and low charge densities making them suitable for protein separation.
• Controlled-pore glass or porous silica
In general, ion exchangers favor the binding of ions of higher charge and smaller radius.
An increase in counter ion (with respect to the functional groups in resins) concentration reduces the retention time. An increase in pH reduces the retention time in cation exchange while a decrease in pH reduces the retention time in anion exchange.
This form of chromatography is widely used in the following applications: water purification, preconcentration of trace components, ligand-exchange chromatography, ion-exchange chromatography of proteins, high-pH anion-exchange chromatography of carbohydrates and oligosaccharides, and others.
Bioaffinity chromatography
This chromatographic process relies on the property of biologically active substances to form stable, specific, and reversible complexes. The formation of these complexes involves the participation of common molecular forces such as the Van der Waals interaction, electrostatic interaction, dipole-dipole interaction, hydrophobic interaction, and the hydrogen bond. An efficient, biospecific bond is formed by a simultaneous and concerted action of several of these forces in the complementary binding sites.
Isocratic flow and gradient elution
A composition of the mobile phase that remains constant throughout the procedure is termed isocratic.
In contrast to this is the so called "gradient elution", which is a separation where the mobile phase changes its composition during a separation process. One example is a gradient in 20 min starting from 10% methanol and ending up with 30% methanol. Such a gradient can be increasing or decreasing. The benefit of gradient elution is that it helps speed up elution by allowing components that elute more quickly to come off the column under different conditions than components which are more readily retained by the column. By changing the composition of the solvent, components that are to be resolved can be selectively more or less associated with the mobile phase. As a result, at equilibrium they spend more time in the solvent and less time in the stationary phase, and therefore they elute faster.
Parameters
Internal diameter
The internal diameter (ID) of an HPLC column is a critical aspect that influences sensitivity and determines the quantity of analyte that can be loaded onto the column. Larger columns are usually seen in industrial applications such as the purification of a drug product for later use. Low ID columns have improved sensitivity and lower solvent consumption at the expense of loading capacity.
• Larger ID columns (over 10 mm) are used to purify usable amounts of material because of their large loading capacity.
• Analytical scale columns (4.6 mm) have been the most common type of columns, though smaller columns are rapidly gaining in popularity. They are used in traditional quantitative analysis of samples and often use a UV-Vis absorbance detector.
• Narrow-bore columns (1-2 mm) are used for applications when more sensitivity is desired either with special UV-vis detectors, fluorescence detection or with other detection methods like liquid chromatography-mass spectrometry
• Capillary columns (under 0.3 mm) are used almost exclusively with alternative detection means such as mass spectrometry. They are usually made from fused silica capillaries, rather than the stainless steel tubing that larger columns employ.
Particle size
Most traditional HPLC is performed with the stationary phase attached to the outside of small spherical silica particles (very small beads). These particles come in a variety of sizes with 5 μm beads being the most common. Smaller particles generally provide more surface area and better separations, but the pressure required for optimum linear velocity increases by the inverse of the particle diameter squared.[1][2][3]
This means that changing to particles that are half as big, keeping the size of the column the same, will double the performance, but increase the required pressure by a factor of four. Larger particles are used in preparative HPLC (column diameters 5 cm up to >30 cm) and for non-HPLC applications such as solid-phase extraction.
Pore size
Many stationary phases are porous to provide greater surface area. Small pores provide greater surface area while larger pore size has better kinetics, especially for larger analytes. For example, a protein which is only slightly smaller than a pore might enter the pore but not easily leave once inside.
Pump pressure
Pumps vary in pressure capacity, but their performance is measured on their ability to yield a consistent and reproducible flow rate. Pressure may reach as high as 40 MPa (6000 lbf/in2), or about 400 atmospheres. Modern HPLC systems have been improved to work at much higher pressures, and therefore are able to use much smaller particle sizes in the columns (<2 μm). These "Ultra High Performance Liquid Chromatography" systems or UHPLCs can work at up to 100 MPa (15,000 lbf/in²), or about 1000 atmospheres. The term "UPLC", though sometimes used is a trademark of Waters Corporation and not the name for the technique in general.

tablet, capsule and ORS production and quality control test

2010-11-14T01:22:00.000-08:00

TABLETS SECTION

According to the Pharmacopeia of India “Pharmaceutical tablets are solid, flat, or biconvex discs, prepared by compressing a drug or a mixture of drugs, with without diluents. They vary in shape and differ greatly in size and weight, depending on the mount of medicinal substances and the intended mode of administration.”
The tablet types and abbreviation commonly employed include
Sugar Coating Tablets (SCT), Film Coated Tablets (FCT) Enteric Coated Tablets (ECT), Chocolate Coated Tablets (CCT), Multiple Compressed Tablets (MCT), Buccal or Sublingual Tablets (B/ST), Dispensing Tablets(DT), Hypodermic Tablets(HT).Time release, sustain release and Prolonged release tablets are designed to make medicament available to the body fluids in the controlled and desired manner and according to the manufacturer’s claim.
 Tablets are the solid dosage forms containing a medicament or mixtures of medicaments and excipient compressed or moulded into solid cylindrical shape having either flat or concave surfaces.

ADVANTAGES
1. Ease of accurate dosage.
2. Good physical and chemical stability.
3. Competitive unit production costs.
4. Release rate of the drug from tablet can be tailored to meet pharmacological requirements.

DISVANTAGES
1. Bioavailability problems because disintegration and dissolution is required before drug is available for absorption.
2. Solid having irritating effect on GIT mucosa posses problems for formulation into tablets.

QUALITY OF A GOOD TABLET:
1. They should be accurate and uniform in weight.
2. The drugs should be uniformly distributed throughout the tablets.
3. The size and shape should be reasonable for easy administration.
4. The tablets should not be too hard that it may not disintegrate in the stomach.
5. There should not be incompatibilities.
6. They should be chemically and physically stable during storage.
7. They should not break during transportation or crumble in the hands of the patient.
8. They should be attractive in appearance.
9. There should not be any manufacturing defects like cracking, chipping or discoloration.
10. After administration it should disintegrate readily.
11. They should be easy and economical in production.

TYPES OF TABLETS:

I. Compressed tablets
1) Coated tablets
a) Sugar coated tablets
b) Film coated tablets
c) Enteric coated tablets
2) Uncoated tablets
a) Multiple compressed tablets
i. Layered tablets
ii. Press coated tablets
b) Prolonged action tablets
c) Solution tablets
d) Effervescent
e) Lozenges
f) Chewable tablets
g) Buccal & sublingual tablets
h) Tablets suppositories pr Inserts.
II. Molded tablets or Tablets Triturates (TT)
1) Dispensing tablets
2) Hypodermic tablets

 Compressed tablets:
A. Oral tablets: - They are placed over the tongue and swallowed with a drink of water or any other suitable liquid takes place from there.
B. Chewable tablets: - These are the tablets, which are required to be broken or chewed in between the teeth before ingestion.
C. Buccal & sublingual tablets:- These tablets are required to be placed belong the tongue(sublingual) or in the sides of the cheeks (buccal) for the slow release of the medicament except in the nitroglycerin and mannitol, hexanitrate tablets which should dissolve in 1 to 2 min to produce immediate effect.
D. Lozenges tablets: - These tablets should not disintegrate in the oral cavity but should dissolve slowly in the mouth to produce continuous effect on the mucous membrane of the throat. In there formulation binding agents are added as to produce slow dissolution.
E. Soluble tablets: - These tablets are required to dissolve completely in the liquid to produce solution of definite concentration. The solution prepared by dissolving the soluble tablets may include mouthwashes, gargles, skin lotion, douches, antibiotics, and certain vitamins.
F. Effervescent tablets: - These tablets along with the active medicament contain other ingredients like SODIUM BICARBONATE, CITRIC ACID, TARTARIC ACID which react in the presence of water liberating carbon dioxide and producing effervescence leading to disintegration of tablet, thus hasten solution formation and increases the palatability. These tablets have the advantage over effervescent powders of being in the tablet dosage form.
G. Vaginal tablet (inserts): - Sometime vaginal suppositories or pessaries are prepared by compression, which are known as vaginal tablet. Antibiotics & steroids are formulated in this way.
H. Implants: - These are the small tablets meant for insertion under the skin by giving a small surgical cut into the skin which is stitched after the insertion of the tablet.
I. Enteric coated tablet: - These are the tablets which are required to be disintegrating in the intestine and not into the stomach.
J. Sustained release action tablets: - These are tablets which after oral administration release the drug at a desired time and prolong the effect of the medicament.
K. Sugar coated tablets: - These are the compressed tablets which are given a sugar coating to mask the objectionable taste and odor of the drug as well as to protect the substance from atmospheric conditions.
L. Film coated tablets: - These are the compressed tablet which are given a thin coating of water soluble material which protect the drug substances from the atmospheric condition.
M. Layered tablets: - These are the compressed tablets in which the granules of incompatible substances are compressed into two or more layers successively in the same tablet. Special tablet making machines are required for making layered tablets.
N. Press coated tablet: - In press coated tablets the granules of incompatible ingredient are compressed around the previously compressed tablet. These types of tablets can also be used for giving enteric coating & sustained release to the medicaments.

Compressed coated tablet Multilayered tablet Sugar coated tablet

TABLET COMPONENT

1) Active ingredient: - The dose of the drug to be administered has a profound effect on the design and formulation of a dosage form.
2) Diluents: - Diluents are fillers designed to make up the required bulk of the tablet when the drug dosage itself is inadequate. Such diluents should meet important criteria, including low cost, good tableting qualities and highly inert. Commonly used diluents are lactose, mannitol, sorbitol and dextrose.

DILUENTS COMMENT
Calcium carbonate Insoluble in water
Glucose Hygroscopic, reducing sugar
Calcium Hydrogen Phosphate Insoluble in water good flow property
Alpha –lactose
Inexpensive, inert and most common diluents
Mannitol
Popular for chewable tablets, freely soluble in water, cool taste
Sodium Carbonate
Freely soluble, used in solution tablet taste problem.
Sucrose
Hygroscopic, sweet taste used in lozenges on conjunction
Microcrystalline cellulose Excellent compression property , highly stable also disintegration property

DILUENTS TRADE NAME
MICROCRYSYALLINE CELLULOSE Arcel, Emcocel
MICROFINE CELLULOSE Elcema
MODIFIED STARCH Sta-Rx
DEXTRATES Emdex
SUCROSE DEXTRIN CO-PRECIPITATE Di – pace
CALCIUM HYDROGEN PHOSPHATE Emcopress
ANHYDROUS LACTOSE DCL
SPRAY DRIED LACTOSE Fast flow, zeparox

3) Binders & Granulating fluids: - These materials are added either in dry or in liquid form during wet granulation to form granules or to promote cohesive compacts for directly compressed tablets. The binders most commonly used are from natural sources, such as starch or cellulose derivatives. The substances mainly used as binders are acacia, gelatin, starch, tragacanth, liquid glucose, Polyvinyl pyrrolidine, cellulose derivative and alginate derivatives.

SUBSTANCE CONCENTRARION COMMENT
Acacia Mucilage Up to 20% Give very hard granules
Glucose Up to 50% Strong adhesive but hygroscopic
Gelatin 5-20% Used as warm solution H forms get on cooling , strong adhesive
Providone (PVP) 2-10% Soluble in water and some organic solvents, can be used for non aq. Granulation
Starch Mucilage 5-10% A common adhesive
Sucrose Up to 70% Hygroscopic, tablet hardness on storage
Tragacanth Mucilage Up to 20% Give hard granules

4) Disintegrant: - For most tablets, it is necessary to over come the cohesive strength introduced into the mass by compression. This process will by done by the disintegrates, by drawing water into the tablets, swelling and causing to burst apart. Such tablet fragment may be critical to the subsequent dissolution of the drug, leads to satisfactory bio- availability. The modern so-called “super” disintegrants which are added to tablets formulations at low levels can assist tablet disintegration by extra granular incorporation and intragranular incorporation. Commonly used disintegranting agents are starch and its derivatives, clay and microcrystalline cellulose.

SUBSTANCE CONCENTRARION (%) COMMENT/ TRADE NAME
Alginic Acid, Sod. Alginate 2-10%
Aluminium magnesium silicate Up to 10% Veegum
Carbon di oxide Created in-situ in effervescent tablet
Sodium carbony methyl cellulose or carmellose, sodium 1-2% Nymcel
Cationic Exchange Resins Up to 10% Amberlite IRP-88
Microcrystalline cellulose(MCC) Up to 10% Avicel
Starch 2-10% Potato and maize starch
Modified starch Starch 1500,sta-Rx1500
Sodium starch glycollate 10-10% Primojet Explotab
Cross carmellose sodium 2% Ac-Di-Si
crospovidone Cross linked povidone, poly plaschone

5) Glidants, Antiadherents and Lubricants: - Glidants are intended to promote flow of the tablet granulation or powder materials by reducing friction between the particles, e.g. talc, corn starch, colloidal silicates etc. Antiadherents have the purpose of reducing sticking or adhesion of any tablet granules or powder to the faces of the punches or to the die wall e. g. talc, magnesium stearate, starch derivatives etc.Lubricants are intended to reduce the tablet friction during tablet ejection between the walls of the tablets and the walls of the die cavity in which tablet is formed e.g. talc, stearic acid, magnesium stearate etc. The degree of film formation of magnesium stearate on the tablet has been studied by applying dissolution techniques and film coating tablet adhesion measurements.

GLIDANTS CONCENTRARION (%) COMMENT
Colloidal Silica 0.1-0.5 % Excellent glidant e. g. Aerosil, Cab-o-sil
Talc 1-2% Insoluble but not hydrophobic

6) Colors, Flavors, Sweeteners: - Colorants do not contribute to therapeutic activity, nor do they improve product bioavailability and stability. Two form of color have typically been used in the tablet preparation. These are FD & C and D & C dyes. Flavors are usually limited to chewable tablet or other tablets intended to dissolve in the mouth. Flavor oil at 0.5-0.75% conc. is added to tablet granules. The use of sweeteners are primarily limited to chewable tablets to evaluate or limit the use of sugar in the tablets e.g. saccharine, mannitol, aspartame etc.
.

SUBSTANCE CONCENTRATION IN TABLETS (%W/W) COMMENT, COMMERCIAL NAME
Fumiric Acid 5% Water soluble
Hydrogenated vegetable oil 0.5- 2.0% Lubritab
Liquid Paraffin Up to 2% Dispersion problem
Magnesium Lauryl Sulphate 1-2% Water soluble
Macragol 4000 & 6000 2-5% Water soluble
Sodium Benzoate 5% Water soluble, taste problems
Sodium lauryl sulphate 0.5-5% Wetting agent often used in conjuction with steaartes
Sodium Stearyl Fumarate 1-2% Soluble in hot water , Pruv
Stearates,Calcium Magnesium Stearic Acid strengt025-1.0%h Very effective lubricants, prolong disintegration time belt, crushing strength

 METHOD OF TABLET PREPRATION:-
The manufacture of granulation for tablet compression may follow one or a combination of three established methods.
a. DIRECT COMPRESSION METHOD: - The methods consist of compressing tablets directly from powdered material without modifying the physical nature of the material itself. Crystalline substances like sodium chloride, sodium bromide, & potassium chloride which possess cohesive and flow properties that make direct compression possible. The vast majority of medicinal agents are rarely, so easy to tablet, however, in addition the compression of a single substance may produce tablets that do not disintegrate. Direct compression materials should posses good flow and compressibility and must be inert, tasteless, able to disintegrate and inexpensive.

b. DRY GRNULATION: - It is also known as” SLUGGING”, “DOUBLE COMPRESSION” OR “RECOMPRESSION” METHOD. It can be used when the tablet ingredient are sensitive to moisture or are unable to withstand elevated temperatures during drying. Under this circumstances, this method provided the tablet ingredients have sufficient inherent binding or cohesive properties. Essential step in this method include weighing, mixing, slugging, dry screening, lubrication & compression. Binders such as spray dried powder or acacia may be added dry to the drug powder allowing formation of a cohesive slug. Lubricant materials are also added (not whole) to reduce powder adhesion to the punches and to facilitate ejection of intact slugs from the dies. Initially large tablets are made as slugs. The slugs are then comminuted through the desirable mesh screen either by hand or, at a large scale, through FITZPATRICK or a similar comminuting mill. Then the remaining lubricants are added to the granulation and after gently blending, the material is compressed into tablets. Examples of materials, which are by this method, are aspirin combination, acetophenetidin, thiamine hydrochloride, ascorbic acid, magnesium hydroxide and other antacid preparations.

c. WET GRANULATION: - This is the oldest and still most widely used method of tablet preparation. Studies on the influence of wet and dry granulation methods on the pore structure of lactose tablets proves wet granulation influence the pore structure over a wide range of tableting pressure while dry granulation influenced only when slugging pressure were high. The powder and mixed tablet constituent are converted to a moist coherent mass by wet screening. The process essentially involves a series of operation such as weighing, mixing, and granulation, screening the damp mass, drying, dry screening, lubrication and finally compression. However, as all of these operations are time bound, problem of reproducing uniform granulation from one lot to the next is the greatest disadvantage of this method. The active ingredients, diluent’s, disintegrant are mixed and blended well. Twin- shell blenders or ribbon blenders may be employed for large scale blending. The blended material is then shifted through a screen of suitable mesh to remove or break the lumps. The solution of binding agent is added to the powder with stirring till the mass attains the consistency of damp snow or brown sugar. A sigma blade mixer or Twin-shell blender may be used in pharmaceutical industry for this purpose. The damp mass is then forced through a 6 or 8 mesh screen. For large quantity FITZPATRICK comminuting mill is used. The granular material thus obtained is dried on trays in hot air oven or in a fluid bed dryer. After drying, the granulation is screened again, followed by compression.

1)Wet Granulation (Schematic Diagram)

A Non GMP Machine for Tablet Compression Showing Various Parts

1. Upper Punch
2. Lower Punch
3. Station

4. Tarrot
• Upper

• Dye

5. Tablet Controller
• Callibre
• Tablet Dropper
6. Hydrolic Pressure
7. Oil pump Pressure
8. Dozer

The basic component or parts of Tablet Compression Machine
1. HOPPER for holding and feeding granules to be compressed
2. DIES that define the size and shape of the tablet.
3. PUNCHES for compressing the granulation within the dies.
4. CAM TRACKS for guiding the movement of the punches.
5. FEED FRAME which has several interconnected compartment, which spread the granulation over a wide area to provide time for the dies to fill.
6. ROLLER
7. TURET
8. BODY
9. DOSE CAPACITY ADJUST SCREW
10. TRAY
11. PULLY
12. VERM
13. PRESSURE REGULARTER
14. OIL BOXES
15. EXHAUST
16. LABLE HOLDER
17. Tablet machine output is affected by (NON GMP MODLE)
(a) No. of tooling stations
(b) No. of compression stations.
(c) Rotational speed of press.

 When the dozer is moved In left then tablet‘s thickness will be decrease and hardness will be increase. When the dozer is moved in right then weight will be increase. The max. Weight of 10 tablets must be 575-615mg only.

TYPES OF PUNCHES
There are 2 type of punches i.e. Moving & Non moving
• FB. Punch - Flat Beveled
• F.B.B.S.Punch –Flat Beveled bisect
• NC. Punch – Narrow concave
• SC. Punch – Shallow concave
• DC. Punch – deep concave
• Caplet punch

Length of punch----------------------------5.25” (Concave Punches)
Upper punch-----------------------------------1/2 “
Lower Punch----------------------------------1”- (it is present under the dies)

(Special Shaped Punches)

PUNCHES DIES

TABLETS COMPERSSION:- Various types of tablet compression machines so used are as follows:
1) Single punch machines
2) Multi punch machines
3) Rotatory machines
4) High speed rotatory machines
5) Multilayer rotatory machines
1) Single punch machines: - In these types of machines one set of dies and punches is fitted and only one tablet can be compressed at one time. They are used when small quantities of tablets are to be prepared. They may be hand operated or power operated and with these machine 60-90 tablets per minutes can be prepared.

2) The rotatory tablet machine: - The rotatory press has more than one set of tooling. The dies and corresponding pairs of punches are arranged around a circular rotating turret. Each individual dies with the lower punching its lowest position, passes under the powder bed which is contained in the feed frame, which in turn fed from the hopper. The die is completely filled under gravity, flow sometime being assisted by rotating fingers in the feed frame. The quantity of solid in the die is adjusted by weight controlling cam. These punches then pass upper punch to descend and the lower punch to rise. Thus the powder is actively compressed from both top and bottom faces. The top punch then withdraws and the lower punch ascends as it passes over an ejection cam.

GMP Model

TECHNICAL SPECIFICATION IN THE ROTATORY TABLET MACHINE
Number of station 10
Output per hour 9600 to 25200
Maximum tablet dia (mm) With D tooling ……….. 23
With B tooling………... 16
Maximum depth of fill (mm ) With D tooling ……….. 20
With B tolling …………17
Operation force 6 Tons
Details of Dies & Punches D tooling & B tooling both are used

3) Multi punch machines: - The construction and working of multi punches machines is exactly similar as that of hand operated single punch machines with difference that a number of dies varying from 2-12 are fitted with the steel frame having exactly the same no. of upper and lower punches. These types of machines are used when the size of tables is small and pressure can be adjusted easily.
4) Multilayer rotatory machines: - With multi layer rotatory tablet machines, tablets having one, two or three layers can be prepared by this method.

Some Important Things Will Be Noted Down While Starting Machine

If pressure increases thickness will be decreases.
If pressure decreases thickness will increases.
If capping is arise speed will be decrease as well as pressure will be decreases.
If sticking will be arise speed decreased and pressure increases.

GMP NONGMP
In tablet counting, tablets are counted 2, 4, 5, 6, 8….. on both side. In tablet counting tablets are counted in series i.e. 1, 2, 3, 4, 5, 6 ..… on both sides.

Tablet Compression Machines used in UPDPL
 In total 6 machines are in use.
 One GMP model, Rotatory tablet machine (double rotation) used of Candane, Ahmedabad.
 This model has 29 stations.
 Output - 300 - 400 per minute.
 Beside 3 single rotatory and 2 rotatory modles are in use.
 Besides 3 single

Rotary press showing position of cycle

(Movement Of Tablets On DOUBLE ROTARY PRESS)

 The Granulation Section has big machines like FLUID BED DRYER, PLANATORY ROTATORY MIXER, SHIFTER, MULTI MILL, and DOUBLE CONE BLENDER.
Information of machine that are related with granules production
I. FLUIDISED BED DRYER (BIG): - Mfd. By Alliance engineering company Bombay
• It is used for uniform and efficient drying of the products
• Fully automatic
• Lifting & tilting device of product container for easy handling.
• Capacity available for 5 kg to 500kg
• Option – steam heated or electric heated blower DOUBLE CONE BLENDER:- Mfd. By Gansons Limited Bombay Capacity – 1500lit.
• Efficient and versatile mixer.
• Ideal for mixing powders and homogeneous lubrication of
• granules
• Moc s.s. 304/316/316 l S.s baffles are provided
• Safety guard provided with limit switch interlocked to motor.
• Capacity 20lit. to 2500lit.
• Automatic loading and unloading facilities available

II. PLANATORY MIXTURE: - Mfd. By Gansons Limited Bombay
• Big, Capacity – 400 lit.
• Small, capacity - 200 lit.

III. MULTI MILL: - Mfd. By Gansons limited Bombay -55
R.P.M. -750 – 3000H. P.–3,
400Volt Sieve Size – 2\5\8mm
• Suitable foe dry granulation/ pulverization/ shredding & chopping of material.
• ulti speed drive for various product grading
• Easy dismantling and cleaning.
• utput 100 to 250 kgs/hr depends upon product & the screen size.
• Moc s. s. 304/316/316 l
• otor – 3hp/1440rpm, rotor dia. 250mm approx
• Beater – 12 nos with knife/ impact edge and 2 scrapper blades.
• Rotor speed – 720/1500/2100/3000 rpm apporx
• Overall dia – 900 l * 800 w* 1700h (in mm)
• CGMP model with documentation (iq, dq, pq, oq) – as option
IV. Mechanical shifter
• Sieve Size – 10

Tablet coating is the application of a coating material to the exterior of a tablet with the intention of conferring benefits and properties to the dosage form over the uncoated variety.

 Types of tablet coating
Three main types are in use:
• Film coating
• Sugar coating
• Press coating

Film coating is the major technique:
All new coated products introduced on to the market are film coated. Sugar coating is the more traditional technology and has seen no real development in recent years. The total output of coated tablet on a global basis, though it is still of some economic importance.

COATING OF TABLETS:
Tablet is usually based on one or more of the following objectives:-
(a) To mask the taste, odor or color of the drug.
(b) To provide physical and chemical protection for the drug.
(c) To control the release of drug from the drug.
(d) To protect the drug from the gastric environment of the stomach with and acid resistant enteric coating.
(e) To improves the pharmaceutical elegance by use of special color and contrasting printing.
THERE ARE THREE PRIMARY COMPONENT INVOLEVE IN TABLET COATING:
1) Tablet properties
2) Coating process
• Coating equipment
• Para meters of coating process
• Facility and ancillary equipment
• Automation in coating process
3) Coating composition

COATING PROCESS:
The principle of tablet coating is relatively simple. Tablet coating is the application of coating composition to moving bed of tablet with the concurrent use of heated air to facilitate evaporation of the solvent. The distribution of coating tablet is accomplished by the movement of the tablet and either perpendicular or vertical to the application of the coating composition.
TYPE OF TABLET COATING:-
1. Sugar coating.
2. Film coating.
3. Enteric coating.

SUGAR COATING:-
The basic coating process involve following steps:
 Sealing
 Sub coating
 Syruping (smoothing)
 Finishing
 Polishing

 Seal coating: - To prevent moisture penetration into tablet core, a seal coat is applied. This is specially needed in pan - ladling process, in which localized over wetting of a portion of the tablet bed occurs. Without seal coat, the over wetted tablet would absorb excess moisture leading to tablet softening or disintegration and effecting physical and chemical stability of final product.

 Sub coating: - The sub coating is applied to round the edges and build up the tablet size. The step consists of applying a sticky binder solution to the tablet followed by a dusting of sub coating powders and then drying.

 Syrup (smoothing/color) coating: - The purpose of step is to cover and fill in the imperfections in the tablet surface caused by sub coating and to impart the desired color to the tablet.

 Polishing: - The desired lusture is obtained in final step of the sugar coating process. The tablets can be polished in the clean standard coating pans or canvas–line polishing pan, by carefully applying powdered wax (bee wax, carnauba wax) or warm solution of these waxes in the naphtha or other suitable volatile oil
E.g.- Ciprofloxacin tablet I.P. 200 mg under the process of simple coating materials talc (75gm), alcohol 4.5 liter titanium, methylene chloride 10.5 liter, HPMC U.S.P. 60 kg of tablets.
o Blower of machine was used for drying the moisture content on the coated tablets.
o Pressurized steam was used to spread dye on tablet for coating.
FORMULATION USED IN SUGAR COATING
SEAL COATING SUB COATING POLISHING
Cellulose acetate phthalate Gelatin Wax, carnauba
Zein Acacia Bee wax, white
Wax sugarcane Wax paraffin
Oleic acid

Steps involved in sugar coating
Step 1:- Slack (1.5%) + alcohol (98.5%) solution 150 – 200 ml for 30 kg lot of tablets Step is doing to check moisture and make tablet hard. Hand pricking method used in it powder is sprayed in the coating pan.
Step 2:- Sub coating: sypup: 20literD.M.water + 40 kg sugar + sodium benzoate is used. Gum syrup: Acacia + gelatin + Calcium Carbonate + talc (5%) + starch (2%) + Titanium dioxide
Step 3:- Talc paste 500gm + syrup + gum syrup 200ml
For finishing of tablet 3-4 coats
Step 4:- Gelatin syrups for shining and D.M. 400 – 500 ml 2-3 coat
Step 5:- Plane syrup 1-1.5 lit. to make smooth color
Step 6: - Color + syrup for tablet polishing bee wax (1%) 500ml, Carnauba wax (1.5%); talc in carbon Tetrachloride/chloroform/benzene was used.
For hexa vitamin cossfera color is used. When a tablet becomes gummy and threads are formed on the hand with touch in Calcium carbonate powders are spread.
FILM COATING:-
Is a thin coating of water soluble material which protects the drug substances from the atmospheric condition?
Two methods are used:
a. Pan pored method
b. Pan spray method
EQUPEMENTS:-
1) Standard coating pan
2) Perforated coating pan or partially perforated drum (Acceela cota and High coater system and Driacoater)
3) Fluidized bed (air suspension) coater.

Capsules are solid doses form usually containing one dose of drug enclosed within a small, water-soluble shell of suitable form of gelatin. Solid substances are enclosed in hard capsules where as soft capsules are suitable for enclosing liquids and semisolids.

Hard Gelatin Capsules
These are referred as dry-filled capsules. They consist of two sections namely the body & caps. Hard gelatin capsules are made from a mixture of gelatin, sugar, water; with/ without suitable colouring agents. Glycerin and sorbitol are commonly used as plasticizers, their exact proportion depending upon the use of capsules and their likely storage conditioned the preservatives are included; generally 0.2% of the mixture of methyl paraben and propyl paraben (4:1) is used.

Process of Hard Gelatin Capsules
Diluents:- Lactose, Mannitol, Sorbitol, starch etc.
Protective /Sorbents:- Oxides, Carbonates of magnesium and Calcium
Glidant: - Talc
Antidusting agents: - Inert edible oils

Filling Equipments
At present, at least nine manufacturers of capsules filling equipment are either located in or selling their products within the United States. Most of the units manufactures outside the United State have local representatives. They are: -
Eli Lilly and Company, Indianapolis, IN
Farmatic SNC, bologna, Italy
Hofliger and karg Waiblingen, Germany
Macofar SAS, Balogna, Italy
mG2 S.p.A., Bologna, Italy
Osaka, Osaka, Japan
Parke-Davis and Company, Detroit, MI
Perry Industries, green Bay, WI
Zanasi Nigris, S.p.A., Bologna, Italy

The Lilly machine describes as

 The empty capsules are fed from the storage hopper though the rectifying unit.
 Into the two piece filling ring Cap Section &Body Section.
Rectification is based on dimensional differences between the outer diameters of the cap and body portion of capsule. As the ring Cap Section &Body Section is rotated, a vacuum is applied on its underside.
 This vacuum seats the bodies into the lower half of the ring, while the cap is retained in the upper portion.
 The two piece of the ring are separated, and the cap containing portion is placed aside.
 The body- containing portion of the ring is placed on a variable speed turntable and is mechanically rotated under the powder hopper
 It contains an auger for the forced delivery of the powder. After one complete rotations of the ring, the powder hopper is removed, and the two segments of the ring Cap Section &Body Section are rejoined.
 The intact ring is positioned in front of the Peg Ring, and the closing plate is pivoted to a position approximately 180 degrees.
 Pneumatic pressure is applied to the Peg ring which forces the capsules body into the cap, and the closing plate holds the caps in position.
 Ejection of the filled capsules from the rings cannot occur with the plate in the closing position. For ejection of the capsules, the pressure is released the closing plate is restored to its original position, and capsules are expelled through the upper portion of the ring.
 Normal closing and ejection occurs with the peg ring in a vertical position with a filled capsules being collected through a chute in a collection chamber.

Precaution of capsules filling

• The body containing ring must be flat across its surface to avoid creating volumetric differences from one area of the ring to another.
• The powder hopper must be properly positioned during the filling operation to avoid uneven powder distribution from the auger. The proper location includes consideration of both the centering of the auger over the ring holes and the parallelism between the lower surface of the hopper and the upper surface of the ring.
• Extreme variation in powder level in the filling hopper can cause uneven powder flow, resulting in excessive fill weight variation.
• The individual rods in the peg ring must fit the rings being used, be of uniform length, and be perpendicular to the closed plate.
• Flow property of the powder being filled must be such that a constant amount of powder is available for delivery from the auger. Diluents and Glidant should be selected with this phase of the operation in mind.

Approximate capacity of CAPSULES vs. NUMBER

S.No. Number Capacity
1 000 950
2 00 650
3 0 450
4 1 300
5 2 250
6 3 200
7
8
4
5 150
100

Teeth13 Teeth14
A B C A B C
X 3.4 2.7 4.3 3.7 2.9 4.6
y 13.6 10.8 17 14.66 11.6 18.3
z 6.8 5.4 8.5 7.3 5.8 9.1
• 480 capsules is formed in 250mg.
• 420capsules is formed in 500mg.
• The name of 100 mg drug is Doxycycillin which is packed in 250mg capsule

1) SEMI AUTOMATIC CAPSULE FILLING MACHINE:-

 The empty capsules are feed into the storage hopper through the rectifying unit into the two piece filling ring (3A & 3B). Rectification is based on the dimensional differences between the outside diameter of the cap and body portion of the capsule. As the ring rotated, a vacuum is applied on its underside. This vacuum seats the bodies into the lower half of the ring, while the cap are retained in the upper portion. The two pieces of ring are separated and the cap containing portions are kept aside.
 The body containing portion of ring is placed on a variable speed turntable and is mechanically rotated under the powder hopper which contain an aurger for the forced delivery of the powder. After one or more complete rotation of the ring, the powder hopper is removed, and two portion of ring are rejoined.
 The intact ring is positioned in front of the peg ring and the closing plate is pivoted to a position approx 180 degrees.
 PNEUMATIC PRESSURE is applied to the peg ring which forged the capsule body into the cap, and the closing plate holds the cap in the position.
 For the ejection of capsule the pressure is released, the closing plate is restored it its original position.
 The capsules are expelled through the upper portion of the ring.
 The filled capsule bring collected through a cute into the collection chamber

2) AUOTOMATIC MACHINE
 The capsules are fed from the storage hopper through individual tubes and rectified into individual two piece side holders on continuous chain.
 The capsule are separated within the two pieces holders by applying vacuum to the lower portion, which pulls the body into it while the cap is retained in the upper holder.
 As the chain retaining blocks progress through the cycle, the cap containing upper holder is moved aside to a recess at the outer end of the conveying holder, exposing the lower holder containing the body.
 The powder is continuously mixed within the powder hopper and is maintained at a constant level prior to discharge.
 The carrying units now are carried under a series of 12 volumetric dosing nozzles each of which picks up the product from a rotating container, first compressing and then ejecting the powder into the capsule bodies.
 The cap container is positioned over the body blocks and closing is accomplished by both upper and lower pins. Ejection is accomplished by compressed air. Each station is equipped with safety device that automatically stop the machine in the event of irregularity. Capsule carrying holder is by air prior to being returned to the rectified station.

WEIGHT INSPECTION RECORD
 Product batch no. batch size
 Machine no. , capsules size operated by.
 Avg. weight M\C started at M\C stopped at
 D.T. variation Wt. of Empty cap.
 Time avg. weight of cap.
 Total no. of capsule No. of containers
 Remarked supervisor date
OBSREVATION OF CAPSULE FILLING SECTION
 The section has a cleaned & humidity controlled room which was centrally air conditioned.
 The capsule comes under various sizes such as 000, 00, 01, 2, 3, 4, & 5.
 Majority of capsule were 0 & 2 no.
 The capsules are properly packed into the strips. E.g.
1) CEPHALEXIN CAPSULE I.P. 250 MG OF AVG. WEIGHT 330mg/ 5mg, THEBATCH SIZE IS 40 LACKS, Batch No. is CF – 1, Size – 2 under process of filling on machine no. SA – 9 with the speed of 33500 – 3360 capsule per hours.

2) AMOXYCILLIN CAPSULE I.P. 500mg, Batch no. AMC5 I , Size no. 0, avg weight 590 mg/ 5mg under process of filling and sealing on machine no. SA – 8.

DIFFICULTIES OF CAPSULE:-
 Deliquescent or hygroscopic powder
 Eutectic mixtures
 Addition of inner powder
 Filling of granular powder
 Use of two capsule
 Liquids

EVALUATION OF CAPSULE
 Uniformity of weight
 Content of active ingredient in capsule
 Disintegration
 Dissolution

PRECAUTIONS INVOLVED IN THE STORAGE OF CAPSULES

 Protection from moisture.
 Store between 15 to 25 degree Celsius with 45 to 55% relative humidity.
 Keep away from any direct source of heat and sunlight.
 Keep bags sealed when not in used.

POLISHING AND SORTING OF CAPSULES
Finished capsules from all filling equipments require some sort of dusting and/or polishing operation before the remaining operations of inspection, bottling, and labeling are completed. Dusting and polishing operations vary according to the type of filling equipment used, the type of powder used for filling, and the individual desire for the finished appearance of the complete capsules.
• Pan polishing: - The Accelacota tablet coating pan may be used to dust and polish capsules. A polyurethane or cheese cloth liner is placed in the pan, and the liner is used to trap the removed dust as well as to impart the gloss to the capsules.
• Cloth dusting: - The bulk filled capsules are rubbed with the cloth that may or may not be impregnated with inert oil. This operation is hand operation, but one that can handle reasonable volumes, and that results in a positive method for removal of resistant materials. In addition, it imparts a somewhat improved gloss to the capsules.
• Brushing: - Capsules are fed under rotating soft brushes, which serves to remove the dust from the capsule shell. This operation must be accompanied by a vacuuming for dust removal. Some materials are extremely difficult to remove by brushing, even to the point of impregnating the brushes and causing scratches or deformation of the capsules.
ROTOSORT: - It is a new filled capsule sorting machine sold by ELI LILLY & company. It is a mechanical sorting device that removes loose powder, unfilled joined capsules, filled or unfilled bodies and loose caps. It can handle up to 150000 capsules per hour, and it can run directly off a filling machine or be used separately.
Seidenader Equipment: - It offers two units that may be used separately or may be combined in the finishing of filled gelatin capsules. A belt is available that presents capsules for visual inspection, and it may include a vacuum system to automatically removed unfilled capsules. Cleaning and polishing machine PM60 may be used to polished capsules. It consists of two lamb’s wool belts moving in opposite directions. The capsules are carried on the lower belt, and both belts are under suction.

Blister packaging is a push through packs (PTP). It is used for many unit dosage forms.

THIS PACKAGING HAS BEEN USED EXTENSIVLY FOR MANY GOOD REASONS:

1) It provides physical protection against shock, vibration & compression etc.
2) It provides barrier protection against water, water vapors, dust, oxygen etc.
3) It provides excellent environmental protection.
4) It is coupled with esthetically pleasing and efficacious appearance.
5) It provides users for convenience child resistant and now temper resistant also.
6) It include anti theft device.
7) There is no chances of agglomeration e. g small object is typically grouped in on pack.

MACHINERY
THERE ARE TWO TYPES OF BLISTER PACKING MACHINE:
1) Automatic blister packaging machine
2) Semiautomatic machine
BLISTER PACKAGING MACHINE is high speed packaging machine designed for packing of product from both side. These machines are very cost effective as they need less electricity as well as durable in nature.

DPB-250E Flat-plate Automatic Blister Packing Machine

PROCESS OF FORMING BLISTER PACKS:-
The blister packs is formed from heat softening a sheet of thermoplastic resin (PVC FILM) and vacuum drawing the soften sheet of plastic into countered mold. After cooling the sheet have been removed from the molds and sent to filling station of packing machine. A semi rigid blister is filled with product and lidding with heat sealable backing materials (printed aluminium foils) .After that it has been cut down by cutters
There are two types of cutters/ blade:
1) Single phase cutter
2) Double phase cutter

In first one there is only one cutter i.e. only one pack can be cut down at a time (10 tablet packs).
In second one there are two cutters i.e. two packs
can be cut down at a time (10, 10 packs).

TYPE OF BLISTER BACKING MATERIAL
Backing material or lidding is either PUSH
THROUGH & PEAL THROUGH or PEALABLE TYPE
FOR push trough the backing material is heat sealable
aluminium foil.
FOR pealable backing material have be used to meet
requirement of child resistant packaging. This type of
packing have a degree of puncture resistant so the child A Blister Pack
could not remove the liding by push as well as it has a
degree of tensile strength to allow the liding to be pulling away from blister.
MATERIAL USED IN BLISTER PACKING
1) PVC(POLY VINYL CHLORIDE)
2) POLY VINYL DICHLORIDE (aclar)
3) POLYPROPYLENE
4) CYCLO OLEFIN COPOLYMER
5) POLYAMYL
6) CELLULOSE ACETATE BUTYRATE(CAB)

1. PVC: They are the cost effective, compactable and can be mould in any shape with minimal shrinkage property. They are of various grades.
2. POLYPROPYLENE:-They are difficult to shape but due to their unstable shrinkage factor and soft nature, they are still used. The main advantage of this system is
having lower moisture absorption coefficient, transparency and glossy appearance.

QUALTY CONTROL TEST FOR BLISTER PACKING
1) BLISTER PACKS LEAK TESTER
2) AUTOMATIC IN LINE TESTER
3) EXTRACTIBLE & LEACHABLE CONTENT TEST
4) MECHANICAL FORCE TESTING
5) VISUAL INSPECTION
6) OFF LINE BLISTER INSPECTION

 BLISTER PACKS LEAK TESTER:- Conventionally blister packs tablet has been tested with methylene blue dye but it was cumbersome and time taking procedure therefore the leak tester has been replace with same. They are validated due to the introduction of sensor inside these leak testers. Swelling of each blister is tested.

 AUTOMATIC IN LINE TESTER: - They are the modified form of the previous one. The compact machine is integrated for 100 percent in line leak detection for automatic sample testing between the body cavity and the lidding foil.

 EXTRACTIBLE & LEACHABLE CONTENT TEST: - Certain instrument such as mass spectrophotometer, gas chromatography is done or used for the estimation of extractible specimen of blister packs.

 VISUAL INSPECTION: - Visual inspection like pin holes, color, shape, shrinkage, print, gloss, quality of printing.

 OFF LINE BLISTER INSPECTION: - An automatic inspection machine is attributed with the load of blister for the inspection of integrity content as per GMP requirement. They are used for the detection of missing tablet, wrong shape of tablet, tablet position, crack tablet, scratched tablet without any embossing, pin hole, incomplete cutting of blister, print defects, less developed cavity, torn pocket etc.

THE ADVANTAGE OF BLISTER PACKAGING OVER
OTHER PACKGING

1) It provides packaging integrity of each product or individual dose.
2) The compliance pack and calendar packs are also possible in blister packaging. and provide visual information to the people.
3) The assurance for other product.

USES
1) Blister packs are used for packaging of tablets, capsule lozenges etc.
2) Blister packaging is used for packaging OTC drug

FIG:- STRIP PACKAGING MACHINE
“A strip packaging is a form of unit dose packaging that is commonly used for the packaging of tablets and capsules. “

A) Strip Packing Machine
1) Primary Packing
M/S Gansons Machine Bombay
Environment Control Specifications
RH-NMT-50%
Temperature NMT 30degrees celcius
Machine Temperature 185degrees celcius
Speed 144strips / minute

2) Secondary Packing
In small cartons
3) Tertiary Packing
In big cartons
Packing defects under stripping
1) Text and color
2) Coding
3) Punctures
4) Empty Pockets
5) Cracking
6) Chipping
7) Denting
8) Stamming on surface
9) Leakage

PROCEDURE Strip Pack

 A strip package is formed by feeding two webs of a heat-sealable flexible film through either a heated crimping roller or a heated reciprocating platen.
 The product is dropped into the pocket formed prior to forming the final set of seals. A continuous strip of packets is formed, generally several packets wide depending on the packaging machine’s limitations.
 The strip of packets is cut to the desired number of packets in length. The strip formed are usually collated and packaged into a folding carton.

Strip Packaging The product sealed between the two sheets of film usually has a seal around each tablet, with perforations usually separating adjacent packets.

MACHINERY
TYPES OF STRIP PACKING MACHINES:-
 Vertical Strip Packaging Machines.
 Horizontal Strip Packaging Machines.
VERTICAL STRIP PACKAGING MACHINES:-
These includes:
 VERTICAL STRIP PACKAGING MACHINE.
 COMPACT VERTICAL STRIP PACKAGER.

“ORS POWDER MIXED AND GRANULATED IN GRANULATION SECTION BY DOUBLE CONE BLENDER MACHINE ONLY PACKING WAS DONE IN THIS SECTION”

 Formula for Oral Rehydration Salt Citrate I.P. 270 g

NaCl IP 3.5g

KCl IP 1.5g

Sodium Citrate 2.9g

Glucose anhydrous 20g

To be dissolved in 1 liter of water

 Procedure
• Milling by multimill and sifting.
• Blending by double cone blender.
• Sifting of blend.
• Goes to Q.C. and packaging section.

 Precautions
• Keep away from moisture.

 Dose
• Age below 2 years 50 to 100 ml (1/4th glass)
• 2-10 years 100- 200 ml (1/2 glass)
• Above 10 years as much as able to drink

 Equipment
Semi automatic ORS sachet filling and sealing machine manufactured by M/S Gansons Bombay; Capacity – 60 sachet in1 minute. Packing done by foil packing.

The department has following chambers:-
• Working laboratory.
• Instrument room.
• Testing laboratory.
• Record room.
• Separate working area for alcoholic/inflammatory processes.
• Sterilizing apparatus room.
• Microbiology laboratory.
• Reproductive laboratory.
• Dispensary.
• Work manager & deputy manager chambers etc.
QUALITY:-
The word “Quality” with reference to a dosage form is comprehensive and refers to characteristics like the potency, uniformity, purity, pharmacological action, stability etc.
Although the responsibility for assuring product quality belongs principally to quality assurance personnel, it involves many departments and disciplines within a company.
QUALITY CONTROL (QC):-
The Quality control process involves:

1) Quarantining of a batch

2) Sampling of drugs from the batch

3) Testing with respect to set parameters

4) Acceptance and Rejection of the batch

5) Destruction of rejected batch

6) Samples of the accepted batches are stored for a period of 3 years

The concept of product quality depends on more than just proper sampling and adequate testing of various components and the finished dosage form.
The Q.C. department of UPDPL is responsible for regulating the quality of product through where industry measures actual quality performance, compares it with standard of national customer company requirement before releasing it to the market for better customer acceptance. UPDPL has a full-fledged quality control department with qualified staff in addition to a commercial testing license.
For drugs supplied to the GOUP an additional level of testing is done at the Analytical Testing Corporation (ATC) at Lucknow. The microbiological testing section is separate from the chemical testing section
Quality Control TESTS:-
In UPDPL following quality control testing is generally employed for assessing the quality of different dosage forms:
 For Tablets
a) Weight Uniformity
b) Hardness
c) Thickness
d) Friability
e) Dissolution Test
f) Disintegration Test
 For Capsules
g) Weight variation
h) Disintegration and dissolution Time
i) Drug content Uniformity
j) Diameter and thickness (outer and inner of cap and shell)
 For Powders (ORS)
k) Particle size
l) Limit test for heavy metals like Arsenic, Lead, Iron, Sulphate etc.
 For Disinfectant and Antiseptics
RWC (Reidel Walker Coefficient) test
Quantitative and Qualitative Analytical Methods are being followed in estimation of authentic nature of pure products and actual and actual quantity of pure, drug content in different dosage form simultaneously.
Quantitative analysis is basically done by Titrimetric method, semi or fully automatic machines for obtaining most accurate results with high precision.
INSTRUMENTS / MACHINES THAT ARE COMMONLY USED PRESENTLY IN UPDPL
1) pH meter Mode L1-10T Euco Pvt. Ltd. Hyderabad, India
2) Remi: ATO mix blender
3) Electronic photo-fluorometer Coleman instruments incmaywood ILL
4) Spectronic 20 Bausch and Lomb
5) HPLC connected with Monitor and Printer
6) Elnova ELCVT constant voltage transformer
7) UV visible spectro-photometer Shimadzu with printer
8) Automatic Potentiometer Titrator AT-38B Spectra lab
9) Colorimeter
10) Polari meter
11) MettlerH5-1A electronic balance
12) Six stage dissolution rate test apparatus IP/BP/USP
13) Friability test apparatus
14) Electronic Balance (Atco)
15) Disintegration Test Apparatus

 WEIGHT VARIATION:- Weigh individually twenty units taken at random or, for single-dose preparations presented in individual containers, contents of twenty units, and determine the average weight (mass). Not more than two of the individual weights (masses) deviate from the average weight (mass) by more than the percentage deviation and none deviates by more than twice that percentage.
Average weight of tablet % deviation
80mg or less 10
X >80mg or <250mg 7.5 X >= 250mg 5
 HARDNESS TEST:-
This test is intended to determine, under defined conditions, the resistance to crushing of tablets, measured by the force needed to disrupt them by crushing.
Apparatus
The apparatus consists of two jaws facing each other, one of which moves towards the other. The flat surfaces of the jaws are perpendicular to the direction of movement. The crushing surfaces of the jaws are flat and larger than the zone of contact with the tablet. The apparatus is calibrated using a system with a precision of 1 Newton.

Fig: Monsanto Hardness Tester
Method
Place the tablet between the jaws, taking into account, where applicable, the shape, the break-mark and the inscription; for each measurement orient the tablet in the same way with respect to the direction of application of the force. Carry out the measurement on 10 tablets, taking care that all fragments of the tablets have been removed before each determination.
This procedure does not apply when fully automated equipment is used.
Expression of the results
Express the results as the mean, minimum and maximum values of the forces measured, all expressed in Newton’s.
 FRIABILITY TEST:- This test is intended to determine, under defined conditions, the friability of uncoated tablets, the phenomenon whereby tablet surfaces are damaged and/or show evidence of lamination or breakage when subjected to mechanical shock or attrition.
Apparatus
Use a drum with an internal diameter between 283 and 291 mm and a depth between 36 mm and 40 mm, made of a transparent synthetic polymer with polished internal surfaces and not subject to static build-up (see Fig.). One side of the drum is removable. The tablets are tumbled at each turn of the drum by a curved projection with an inside radius between 75.5 mm and85.5 mm that extends from the middle of the drum to the outer wall. The drum is attached to the horizontal axis of a device that rotates at 25 ± 1 r/m. Thus, at each turn the tablets roll or slide and fall onto the drum wall or onto each other.

Method
For tablets weighing up to 0.65 g each, take a sample of twenty tablets; for tablets weighing more than 0.65 g each, take ten tablets. Place the tablets on a sieve no. 1000 and remove any loose dust with the aid of air pressure or a soft brush. Accurately weigh the tablet sample and place the tablets in the drum. Rotate the drum 100 times and remove the tablets. Remove any loose dust from the tablets as before. If no tablets are cracked, split or broken, weigh the tablets to the nearest milligram.
Generally the test is run once. If the results are doubtful or if the mass loss is greater than 1%, repeat the test twice and determine the mean of the three tests. A maximum loss of 1% of the mass of the tablets tested is considered to be acceptable for most products.
For tablets having a diameter of 13 mm or greater, problems of reproducibility may be encountered due to frequent irregular tumbling. In such cases, adjust the drum so that the tablets may fall freely and do not bind together when lying next to each other, adjusting the drum so that the axis forms a 10° angle with the base is usually satisfactory.
Expression of the results: The friability is expressed as the loss of mass and it is calculated as a percentage of the initial mass.

Friability Test Apparatus

Operating procedure:
1. Ensure that instrument is clean &free from dust.
2. Accurately Weigh 10 Tablets.
3. Open the apparatus from one removable side of drum.
4. Transfer the tablets in it& close the drum tightly.
5. Switch ON the instrument.
6. Place the timer switch to min. position.
7. Wait till rotation stop.
8. Open the drum & remove any loose dust or broken small pieces of tablets.
9. Weigh the remaining tablets.
10. Switch OFF the instrument when not in use.

Wt. of tablets (before rotation-after rotation) x 100
% Friability = Wt. of tablets before rotation

Calibrator: - Start the rotation of drum as per operating Procedure
a) Count the no. of rotation for exactly 4 min.
b) Repeat the counting for 2 to 3 times.
c) Determine the avg. RPM.
d) Avg. RPM should 24-26 Revolution/minute.
e) Calibration frequency –Half Yearly.

 DISSOLUTION TEST APPARATUS:-
Digital six stage Dissolution Test Apparatus (I.P, B.P and U.S.P)

Standard operating procedure:

1. Ensure that instrument is clean &free from dust. Ensure the instrument is connected to stabilize power supply.
2. Check water level of bath from mark given at the side of bath of apparatus and fill up to mark if necessary.
3. Deacerate the dissolution medium.
4. Check pH of the medium at 37 +/- 0.5 adjust the pH +/- 0.05 unit of pH specified in monograph. Incase of buffered solution.
5. Filled the stated volume of dissolution medium in cleaned bowl of apparatus.
6. Switch ON the power. Instrument will initialize itself The display will show temp. / Time & RPM.
7. For setting RPM press RPM key from the front panel. Settling screen fort the RPM will be displayed RPM can be set from 50-150.
8. After setting the desire speed for the stirrer status “START” or “STOP” by using “START” or “STOP” key respectively.
9. Temperature is automatically controlled at 37˚C by inbuilt thermostat sensor.
10. Current temperature will display on panel.
11. For sample interval setting press the TIME key from the panel. This will display the screen for setting the sample time can be set from 00 minute to 99 hr 59 minutes.

 DISINTEGRATION TEST:-

The disintegration test determines whether tablets or capsules disintegrate within a prescribed time when placed in a liquid medium under the prescribed experimental conditions.
Disintegration is considered to be achieved when no residue, except fragments of undissolved tablet coating or of capsule shell, remains on the screen of the test apparatus or adheres to the lower surface of the disc if a disc has been used; if any other residue remains, it consists of a soft mass having no palpably firm, unmoistened core.

Apparatus : A rigid basket-rack assembly supporting six cylindrical glass tubes 75.0 to 80.0 mm long, 21.5 mm in internal diameter and with a wall thickness of about 2 mm.

Disintegration Test Apparatus
i. Procedure starts up
 Ensure that instruments are free from dust.
 Connect the three pin plug to main 230 volt single phase A.C.
 Put the glass beaker (1000 ml capacity.) on the hot plate on the top of units.
 Put the thermometer (range 0to50˚c) at the placement for in basket rack assembly.
 Fill the beaker with warm water /medium at 37˚c +/-2˚c so that the volume of water /medium in such the wire mesh at its height point is t least 25mm below the surface of liquid 2 at its lower point is at least 25mm above the bottom of the beaker.
 Maintain temperature of water /medium at 37˚c +/-2˚c with help of thermostatic device.
ii. Operational procedure
 Switch ‘ON’ the main switch on front panel.
 Check the calibration status of instruments.
 Put one tablets/capsules in each of six-glass tube add the dish to each tube.
 Switch on the motor switch to operate the apparatus for specified time and immediately start the stopwatch.
 When all the tablets / capsules pass out from the mash top the stopwatch and stop the disintegration apparatus.
 The time will be shown on stopwatch.
 Record the time at which all six tablets get disintegrated.
 Inform the Q.C head, if tablets are not getting disintegrated. Within specified /set time.
 In case of failure repeat the test with addition of 12 units. All the tablets should comply with required.
 Clean the basket & beaker.
iii. General case and Precaution
 The sequence shaft should be lubricated with mobile oil once in a week.
 The equation should never be switch ‘ON’ unless beaker filled with water or kept on hot plate
 Do not holds square bar while, it is moving otherwise the gear will be damaged.

SPECTROPHOTOMETER

1. Open the display unit and turn on the main switch.
2. Initialization takes place about 2 min and instrument comes in “mode condition” or “ Previous Mode”.
PHOTOMETRIC MODE : -
1. Press I number key of “Mode” for photometric mode and it will show wavelength and absorbance.
2. Press “go to wavelength key, enter required wavelength and press enter key.
3. Fill both the cuvett (UV/ Visible as per requirement) with the blank and put in their place.
4. Close the lid and press “AOTO ZERO” key to match the cuvett.
5. Fill R.S. or sample solution in the cuvett.
6. Close the lid absorbance display on screen.
7. On pressing ‘F3’ key measurement screen will appear in table form.
8. Fill the K value by pressing “F4” key and press in table form.
9. On pressing “START” key, % of content will appear on screen.
Press “PRINT” and get the printed report

POLARIMETER

Ensure that the instrument and all its part are clean and free from dust.
1. Switch on the instrument and let sodium lamp illute to its maximum brightness.
2. Set the alignment of the sodium lamp compartment to the optical bench.
3. Ensure that all the settings are done in the Zero- Zero positions.
4. Open the polarimeter tube compartment and place the polarimeter tube which is filled with sample in such a way as to avoid air bubbles.
5. Specific attention should be paid to temperature control of the solution and of the polarimeter.
6. Note the observation reading and also perform a blank determination in the similar manner.
7. Observation are done by observing through telescope when the half dark and half light portion of the circle has in equilibrium.
8. This half dark and half light portion is matched with a knob by rotating it clockwise/ anticlockwise direction. It is also defined as dextro +) or laevo (-) rotatory respectively.
10.Clean the instrument and keep under cover when not in use.
PRECAUTION:-
1. Proper handling of the instrument.
2. Temperature should be maintained.

H.P.L.C. OPERATING PROCEDURE
1. Turn ‘ON’- (1st) Binary pump switch (2nd) detector switch.
2. See detector screen for successful calibration (do accordingly).
3. Turn ‘ON’ C.P.U. and monitor switches.
4. Select ‘Breeze’ system. wait till booting is over. Check all configurations are on the monitor screen.
5. Select operator name from manage Breeze, change prefilter, guard tube and column (if necessary)

6. Remove the air from the pump through syringe and run acetonitrile/ Methanol at 0.2 ml/ minute flow rate for preconditioning the column. (2 hours)
7. Filter fresh distilled water by membrane filter and degassed. Prepare mobile phase, filter and degassed. Prepare Diluting solvent, filter and degassed.
8. Weigh R.S. and sample accurately and prepare as per monograph.
9. Run mobile phase at flow rate 1.0 ml/ minute (or as per method) till constant pressure is achieved.
10. Select method and equililibrate Mobile Phase till straight line/ curve is achieved. Check wavelength on detector screen.
11. Abort and click injection. Filter R.S name run etc and click O.K. Inject R.S. through injector. Give 3 to 5 replicate injections. Check R.S.D. though wizard.
12. Inject sample all batches one by one as R.S.
13. Calculate drug % by comparing R.S. peak area with sample peak area. Take out print.
14. After work is over do washing of membrane filter vessel, syringe, needle, etc. by H.P.L.C. water. And by hot water thoroughly.

The Marketing setup of the company can be classified in two division i.e. Institutional Sales and Open Trade Marketing.

Institutional Sales.
UPDPL is basically established to cater the need of U.P. Govt. Health Deptt. The U.P. Govt. Health Deptt. has also reserved 39 items in favour of UPDPL which are exclusively to be purchased from UPDPL. The U.P. Govt. Health Deptt. is purchasing the medicines upto the extent of Rs. 25.00 crores per annum as centralized orders. UPDPL is successfully executing the orders to Addl. Director, levels with their entire satisfaction in respect of quality and quantity. On delivery of the goods at A.D. Mandals the Marketing team of Institutional Sale is being deputed for verification of the bills for onward payment from the office of Director (Stores), Medical & Health Services, Swasthya Bhawan , Lucknow.

Apart from the above UPDPL is also catering the entire need of all periphery officers i.e. CMO,CMS (Male/Felame), DTOs etc. UPDPL has developed a team for Institutional Sale of 9 – 10 persons who are deployed in the various distt. H.Qs. to collect the requirement and timely execution of the orders to the periphery officers.

In order to increase capacity utilization of the plant UPDPL have expand their marketing activities in other states also. UPDPL have have secured recognition in different states like Jharkhand, M.P., Andra Pradesh., Gujrat and Pondicherry etc. UPDPL is participating in the tender enquiries floated by the different Sate Govt. as well as Central Govt. Institutions/Govt. 5-6 products have been approved by the E.S.I.C, New Delhi on the basis of 1st lowest and IInd lowest. The Andhra Pradesh Govt. have also approved 2 produdcts on the basis of the lowest rates.

The executions of the orders of other state are being made by the company through Distributors/ C& F net work.

natural polymer

2010-11-13T12:23:00.001-08:00

Natural-based polymers for biomedical applications

examines the sources, processing and properties of natural based polymers for biomedical applications
- explains how the surfaces of polymer based biomaterials can be modified to improve their functionality
- discusses the use of natural based polymers for hydrogels in tissue engineering, and inparticular natural gelling polymers for encapsulation and regenerative medicine
- summarises the use of natural based polymers as delivery systems for drugs, hormones, enzymes and growth factors

Polymers from natural sources are particularly useful as biomaterials and in regenerative medicine, given their similarity to the extracellular matrix and other polymers in the human body. This important book reviews the wealth of research on both tried and promising new natural-based biomedical polymers, together with their applications as implantable biomaterials, controlled-release carriers or scaffolds for tissue engineering.

The first part of the book reviews the sources, processing and properties of natural-based polymers for biomedical applications. Part two describes how the surfaces of polymer-based biomaterials can be modified to improve their functionality. The third part of the book discusses the use of natural-based polymers for biodegradable scaffolds and hydrogels in tissue engineering. Building on this foundation, Part four looks at the particular use of natural-gelling polymers for encapsulation, tissue engineering and regenerative medicine. The penultimate group of chapters reviews the use of natural-based polymers as delivery systems for drugs, hormones, enzymes and growth factors. The final part of the book summarises research on the key issue of biocompatibility.

Introduction of patural polymer- In the area of drug delivery, various polymers are involved. The earlier polymers were natural in origin. The natural polymers were found to be fraught with many formulation Problems such instability, irreproducibility, changes in aesthetics on storage, uncontrollable Formulation characteristics, etc. As a result new designer molecules were sought for to solve Some of the problems. Some of the natural polymers were largely polysaccharide gums such as acacia, guar, xanthan, agar, tragacanth, etc. These may have their origin plant, seaweed or even fungi. Some bacteria are known to produce polysaccharides that may be useful in medical and pharmaceutical practices. A few polymers may be of animal origin such as gelatin, serum albumin, liposomes, etc. On the other hand, synthetic polymers are either modified from natural polymers or completely synthesized from synthetic monomers. They process properties that seem to relatively address the problems of instability, irreproducibility, changes in aesthetics on storage, uncontrollable formulation characteristics. The environment of use in the body is often considered in the preparation of these polymers. Good examples are the derivates of the acrylic resins, vinyl polymers, cellulose polymers, etc. Various aspects of these two classes of polymers are presented in this chapter.

Natural Biopolymers in Gene therapy Delivery
Chukwuemeka S. Nworu, Edward C. Nwanegbo, and Charles O. Esimone

Effective delivery of therapeutic genes to target cells is an essential goal of all innovative gene therapy endeavours and recombinant vaccine technology. Current use of viral vectors in achieving this goal has been associated with minimal success and plethora of unwanted adverse events. As a result, there is an ongoing search for suitable vector platforms for the delivery of therapeutic genes to target cells. Such agent should be easily manipulated to accommodate small and large gene inserts and safely deliver Transgenes. This will ensure effective expression of the gene in target cells. The resulting optimal expression of this gene may correct defective or deficient gene in individuals receiving gene therapy. This chapter examines the applications of biopolymers as non-viral gene delivery vectors either alone or as copolymers.

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Particulate Drug Delivery: Recent Applications of Natural Biopolymers
Anthony A. Attama and Philip F. Builders

Polymers fall into three broad categories: natural, semi-synthetic and synthetic. Polymers are widely used in pharmaceutical systems as drug carriers, adjuvants, suspending and emulsifying agents. The word "polymer" which means "many parts", is derived from the Greek words poly, meaning "many," and meros, meaning "parts". Polymers are widely found in nature and occur in many forms. The human body contains many natural polymers such as proteins and nucleic acids, while cellulose is the main structural component of plants. Cellulose, starch, lignin, chitin, and various polysaccharides are of natural origin. These materials and their derivatives offer a wide range of properties and applications in drug delivery. Natural polymers are usually biocompatible and biodegradable. In this chapter, sources and applications of natural biopolymers in particulate drug delivery systems such as microparticles and nanoparticles, which are currently widely investigated as drug delivery systems, were discussed.

Challenges of the Use of Natural Biopolymers in Drug Delivery
N.C. Obitte and E.O. Omeje

Drug delivery and pharmacokinetics have remained important components of therapeutic and biomedical practice for many decades. In recent time, the world has witnessed rapid progress in developments of different drug delivery protocols, especially as it regards the use of degradable biopolymers. This became a viable research and economic venture with parallel progress in inter-related fields of biomaterial science, biotechnology, nanotechnology and pharmacology. Recent advances in material science, biomaterial development and tissue engineering are changing the face of medicine in the present age. Biopolymers and drug delivery systems offer the “ideal” conceptual framework for improving the efficacy of existing drug formulations and developing new treatments. Interestingly, there are extensive researches so far carried out in the area of biodegradable materials for controlled release of drug which circumvents the need for removal of nondegradable drug-depleted devices. Many biodegradable polymers have been evaluated for their suitability as matrix for drugs, including polyesters, polycarbonates, natural and synthetic polyamides, phosphate esters, polyphosphazenes and polyanhydrides. Current and novel drug delivery approaches involve the application of these polymers in a variety of devices, including biodegradable polymer shape-memory polymers, targeted nanoparticle conjugates and miniaturized drug delivery devices. These approaches have greatly improved the delivery of drugs to target sites that would have been ordinarily impossible by conventional therapeutic routes. In this chapter, we will discus some key recent and relevant advances in the use of biopolymers for drug delivery. Thereafter, the challenges still ahead will be presented. In all, biopolymers promise rewarding prospects for the world in this 21st century and beyond.

Particulate Drug Delivery: Recent Applications of Natural Biopolymers
Anthony A. Attama and Philip F. Builders

Polymers fall into three broad categories: natural, semi-synthetic and synthetic. Polymers are widely used in pharmaceutical systems as drug carriers, adjuvants, suspending and emulsifying agents. The word "polymer" which means "many parts", is derived from the Greek words poly, meaning "many," and meros, meaning "parts". Polymers are widely found in nature and occur in many forms. The human body contains many natural polymers such as proteins and nucleic acids, while cellulose is the main structural component of plants. Cellulose, starch, lignin, chitin, and various polysaccharides are of natural origin. These materials and their derivatives offer a wide range of properties and applications in drug delivery. Natural polymers are usually biocompatible and biodegradable. In this chapter, sources and applications of natural biopolymers in particulate drug delivery systems such as microparticles and nanoparticles, which are currently widely investigated as drug delivery systems, were discussed.

Polysaccharides as carriers of bioactive agents for medical applications
P Pawar, W Jadhav, S Bhusare and R Borade, Dnyanopasak College, India, S Farber, D Itzkowitz and A Domb, The Hebrew University, Jerusalem, Israel
- Introduction
- Starch
- Cellulose
- Heparinoid (sulfated polysaccharides)
- Dextran
- Pectin
- Arabinogalactan
- Drug conjugated polysaccharides
- Dextrans
- Mannan
- Pullulan
- Polysaccharides macromolecule-protein conjugates
- Cationic polysaccharides for gene delivery
- Diethylaminoethyl-dextran
- Polysaccharide-oligoamine based conjugates
- Chitosan
- Applicatons of polysaccharides as drug carriers
- Applications of dextran conjugates
- Site-specific drug delivery
- Pectin drug site specific delivery
- Liposomal drug delivery
- References
Purification of naturally occurring biomaterials
M N Gupta, Indian Institute of Technology Delhi, India
- Introduction
- Classes of naturally occurring biomaterials
- Downstream processing of small molecular weight natural products
- Purification strategies for proteins
- Purification of lipids
- Purification of polysaccharides
- Purification of nucleic acids
- Purification of complex biomaterials
- Future trends
- Sources of further information
- Acknowledgements
- References
Processing of starch-based blends for biomedical applications
R A de Sousa, V M Correlo, S Chung, N M Neves, J F Mano and R L Reis, University of Minho, Portugal
- Introduction
- Starch
- Starch-based blends
- Conclusions
- References
Controlling the degradation of natural polymers for biomedical applications
H S Azevedo, T C Santos and R L Reis, University of Minho, Portugal
- Introduction
- The importance of biodegradability of natural polymers in biomedical applications
- Degradation mechanisms of natural polymers and metabolic pathways for their disposal in the body
- Assessing the in vitro and in vivo biodegradability of natural polymers
- Controlling the degradation rate of natural polymers
- Concluding remarks
- Acknowledgements
- References
Smart systems based on polysaccharides
M N Gupta and S Raghava, Indian Institute of Technology Delhi, India
- What are smart materials?
- Chitin and chitosan
- Alginates
- Carrageenans
- Other miscellaneous smart polysaccharides and their applications
- Polysaccharide-based composite materials
- Future trends
- Acknowledgement
- Sources of further information and advice
- References

PART 2 SURFACE MODIFICATION AND BIOMIMETIC COATINGS

Surface modification of natural-based biomedical polymers
I Pashkuleva, P M López-Pérez and R L Reis, University of Minho, Portugal
- Introduction
- Some terms and classifications
- Wet chemistry in surface modification
- Physical methods for surface modification
- Grafting
- Bio-approaches: mimicking the cell-cell interactions
- Future trends
- Acknowledgments
- References
New biomineralization strategies for the use of natural-based polymeric materials in bone-tissue engineering
I B Leonor, S Gomes, P C Bessa, J F Mano and R L Reis, University of Minho and M Casal, CBMA - Molecular and Environmental Biology Center, University of Minho, Portugal
- Introduction
- The structure, development and mineralization of bone
- Bone morphogenetic proteins in tissue engineering
- Bio-inspired calcium-phosphate mineralization from solution
- General remarks and future trends
- Acknowledgments
- References
Natural-based multilayer films for biomedical applications
C Picart, Université Montpellier, France
- Introduction
- Physico-chemical properties
- Different types of natural-based multilayer films for different applications
- Bioactivity, cell adhesion, and biodegradability properties
- Modulation of film mechanical properties
- Future trends
- Sources of further information and advice
- References
Peptide modification of polysaccharide scaffolds for targeted cell signaling
S Lévesque, R Wylie, Y Aizawa and M Shoichet, University of Toronto, Canada
- Introduction
- Polysaccharide scaffolds in tissue engineering
- Peptide immobilization
- Measurement
- Challenges associated with peptide immobilization
- Tissue engineering approaches targeting cell signalling
- References

PART 3 BIODEGRADABLE SCAFFOLDS FOR TISSUE REGENERATION

Scaffolds based on hyaluronan derivatives in biomedical applications
E Tognana, Fidia Advanced Biopolymers s.r.l., Italy
- Introduction
- Hyaluronan
- Hyaluronan-based scaffolds for biomedical applications
- Clinical applications
- Future trends
- Sources of further information and advice
- References
Electrospun elastin and collagen nanofibers and their application as biomaterials
R Sallach and E Chaikof, Emory University/Georgia Institute of Technology, USA
- Introduction
- Electrospinning as a biomedical fabrication technology
- Generation of nanofibers with controlled structures and morphology
- Generation of collagen and elastin small-diameter fibers and fiber networks
- Biological role of elastin
- Generation of crosslinked fibers and fiber networks
- Multicomponent electrospun assemblies
- Future trends
- References
Starch-polycaprolactone based scaffold for bone tissue engineering
M E Gomes, J T Oliveira, M T Rodrigues, M I Santos, K Tuzlakoglu, C A Viegas, I R Diaz and R L Reis, University of Minho, Portugal
- Introduction
- Starch+e-polycaprolactone (SPCL) fiber meshes
- SPCL-based scaffold architecture, stem cell proliferation and differentiation
- In vivo functionality of SPCL fiber-mesh scaffolds
- Cartilage tissue engineering using SPCL fiber-mesh scaffolds
- Advanced scaffold design for bone tissue engineering
- Nano/micro fiber combined scaffold - innovative architecture
- Conclusions
- References
Chitosan-based scaffolds in orthopaedic applications
K Tuzlakoglu and R L Reis, University of Minho, Portugal
- Introduction: Chemical and physical structure of chitosan and its derivatives
- Production methods for scaffolds based on chitosan and its composites or blends
- Orthopaedic applications
- Conclusions and future trends
- Acknowledgements
- References
Elastin-like systems for tissue engineering
J Rodriguez-Cabello, A Ribeiro, J reguera, A Girotti and A Testera, Universidad de Valladolid, Spain
- Introduction
- Genetic engineering of protein-based polymers
- Genetic strategies for synthesis of protein based polymers
- State-of-the-art in genetically-engineered protein-based polymers (GEBPs)
- Elastin-like polymers
- Self-assembly behaviour of peptides and proteins
- Self-assembly of elastin-like polymers (ELPs)
- Biocompatibility of ELPs
- Biomedical applications
- ELPs for drug delivery
- Tissue engineering
- Self-assembling properties of ELPs for tissue engineering
- Processability of ELPs for tissue engineering
- Future trends
- References
Collagen-based scaffolds for tissue engineering
G Chen, N Kawazoe and T Tateishi, National Institute for Materials Science, Japan
- Introduction
- Structure and property of collagen
- Collagen sponge
- Collagen gel
- Collagen–glycosoaminoglycan (GAG) scaffolds
- Acellularized scaffolds
- Hybrid scaffolds
- Future trends
- References
Polyhydroxyalkanoate and its potential for biomedical applications
P Furrer and M Zinn, EMPA and S Panke, Swiss Federal Institute of Technology (ETH), Switzerland
- Introduction
- Biosynthesis
- Chemical digestion of PHA-biomass
- Purification of PHA
- Potential applications of PHA in medicine and pharmacy
- Conclusions and future trends
- References
Electrospinning of natural proteins for tissue engineering scaffolding
P I Lelkes, M Li, A Perets, L Lin, J Han and D Woerdeman, Drexel University, USA
- Introduction
- The electrospinning process
- Electrospinning natural animal polymers
- Electrospinning blends of synthetic and natural polymers
- Electrospinning novel natural ‘green’ plant polymers for tissue engineering
- Soy proteins
- Corn zein
- Wheat gluten
- Blends of synthetic and plant proteins
- Cellular responses to electrospun scaffolds: does fiber diameter matter?
- Conclusions and future trends
- Sources of further information and advice
- References

PART 4 NATURALLY-DERIVED HYDROGENS: FUNDAMENTALS, CHALLENGES AND APPLICATIONS IN TISSUE ENGINEERING AND REGENERATIVE MEDICINE

Hydrogels from polysaccharide-based materials: fundamentals and applications in regenerative medicine
J T Oliveira and R L Reis, University of Minho, Portugal
- Introduction: definitions and properties of hydrogels
- Applications of hydrogels produced from different polysaccharides in tissue engineering and regenerative medicine
- Agarose
- Alginate
- Carrageenan
- Cellulose
- Chitin/chitosan
- Chondroitin sulphate
- Dextran
- Gellan
- Hyaluronic acid
- Starch
- Xanthan
- Conclusions
- References
Alginate hydrogels as matrices for tissue engineering
H Park and K-Y Lee, Hanyang University, South Korea
- Introduction
- Properties of alginate
- Methods of gelling
- Application of alginate hydrogels in tissue engineering
- Summary and future trends
- References
Fibrin matrices in tissue engineering
B Tawil, H Duong and B Wu, University of California, USA
- Introduction
- Fibrin formation
- Fibrin use in surgery
- Fibrin matrices to deliver bioactive molecules
- Fibrin - cell constructs
- Mechanical characteristics of fibrin scaffolds
- Future trends
- Conclusions
- References
Natural-based polymers for encapsulation of living cells: fundamentals, applications and challenges
P De Vos, University Hospital of Groningen, The Netherlands
- Introduction
- Approaches to encapsulation; Materials and biocompatibility issues
- Physico-chemistry of microcapsules and their biocompatibility
- Immunological considerations
- Conclusions and future trends
- Sources of further information and advice
- References
Hydrogels for spinal cord injury regeneration
A J Salgado, N Sousa, N A Silva, N M Neves and R L Reis, University of Minho, Portugal
- Introduction
- Brief insights on central nervous system biology
- Current approaches for SCI repair
- Hydrogel-based systems in SCI regenerative medicine
- Conclusions and future trends
- Acknowledgments
- References

PART 5 SYSTEMS FOR THE SUSTAINED RELEASE OF MOLECULES

Particles for controlled drug delivery
E T Baran and R L Reis, University of Minho, Portugal
- Introduction
- Novel particle processing methods
- Hiding particles: the stealth principle
- Finding the target
- Delivery of bioactive agents at the target site and novel deliveries
- Viral delivery systems
- Conclusions
- Acknowledgements
- References
Thiolated chitosans in non-invasive drug delivery
A Bernkop-Schnürch, Leopold-Franzens University, Austria
- Introduction
- Thiolated chitosans
- Properties of thiolated chitosans
- Drug delivery systems
- In vivo performance
- Conclusions
- References
Chitosan-polysaccharide blended nanoparticles for controlled drug delivery
J M Alonoso and F M Goycoolea, Universidad de Santiago de Compostela, Spain and I Higuera-Ciapara, Centro de Investigación en Alimentación y Desarrallo, Mexico
- Introduction
- Polysaccharides in nanoparticle formation
- Nanoparticles constituted from chitosan
- Drug delivery properties and biopharmaceutical applications
- Hybrid nanoparticles consisting of chitosan and other polysaccharides
- Future trends
- Sources of further information and advice
- Acknowledgements
- References

PART 6 BIOCOMPATIBILITY OF NATURAL-BASED POLYMERS

In vivo tissue response to natural-origin biomaterials
T C Santos, A P Marques and R L Reis, University of Minho, Portugal
- Introduction
- Inflammation and foreign-body reactions to biomaterials
- Role of host tissues in biomaterials implantation
- Assessing the in vivo tissue responses to natural-origin biomaterials
- Controlling the in vivo tissue reactions to natural-origin biomaterials
- Final Remarks
- Acknowledgements
- References
Immunological issues in tissue engineering
N Rotter, Ulm University, Germany
- Introduction
- Immune reactions to biomaterials
- Host reactions related to the implant site
- Immune reactions to different types of cells
- Immune reactions to in vitro engineered tissues
- Immune protection of engineered constructs
- Strategies directed towards reactions to biomaterials
- Strategies directed towards reactions to implanted cells
- Future trends
- Sources of further information and advice
Biocompatibility of hyaluronic acid: from cell recognition to therapeutic applications
K Ghosh, Children’s Hospital and Harvard Medical School, USA
- Introduction
- Native hyaluronan
- Therapeutic implications of native hyaluronan
- Engineered hyaluronan
- Implications for regenerative medicine
- Conclusions
- Future trends
- References
Biocompatibility of starch-based polymers
A P Marques, R P Pirraco and R L Reis, University of Minho, Portugal
- Introduction
- Starch-based polymers in the biomedical field
- Cytocompatibility of starch-based polymers
- Immunocompatibility of starch-based polymers
- Conclusions
- Acknowledgments
- References
Vascularisation strategies in tissue engineering
M I Santos and R L Reis, University of Minho, Portugal
- Introduction
- Biology of vascular networks - angiogenesis versus vasculogenesis
- Vascularization: the hurdle of tissue engineering
- Neovascularization of engineered bone
- Strategies to enhance vascularization in engineered grafts
- In vivo models to evaluate angiogenesis in tissue engineered products
- Future trends
- Sources of further information and advice
- References

The word polymer is name comes from greek words. Polymer is a substance which consists of molecules which are at least around multiples of low molecules weight units. Monomer is a small molecule which joins with every other from a polymer. The types of natural polymers follow.

Types of Natural Polymers

The natural polymers obtained from nature are known as natural polymers. There are five types available in natural polymers.

· Starch

· Cellulose

· Proteins

· Nucleic Acid

· Natural rubber

Starch

It is a polymer of glucose. It is a principal food store of plants.

Cellulose

It is also polymer glucose. It is principal structural material of the plants. Both starch and cellulose are produced by plants through photosynthesis.

Proteins

These are polymers of alpha amino acids. They have usually 20 to 100 alpha amino acids joined together in a highly organized arrangement. These are building group of animals.

Nucleic Acids

These are polymers has a variety of nucleotides. RNA and DNA are ordinary nucleotides.

Natural rubber

It is a polymer of unsaturated hydrocarbon, 3 butadiene known as isoprene. It is finding from latex of rubber trees.

Examples for Natural Polymer

1. Starch: Starch is a best example of natural polymer. Starch is also one of a polymer of glucose. It is a chief food reserve of plants.

2. Cellulose: Plants are made of a polymer is called cellulose. It is also one of a polymer of glucose. It is one of the examples of natural polymer. It is a chief structural material of the plants. Both starch and cellulose are produced by plants during photosynthesis.

3. Proteins: These are polymers of α-amino acids. They have generally 20 to 100 α-amino acids joined together in a highly organized arrangement. These are building block of animals. It is an example of natural polymer.

4. Nucleic acids: These are polymers of various nucleotides. RNA and DNA are common nucleotides.

5. Natural rubber: It is a polymer of unsaturated hydrocarbon, 2-methyl-1, 3-butadiene, called isoprene. It is obtained from latex of rubber trees. Natural rubber is a gummy material, has poor elasticity. It becomes permanently deformed when stretched. However, a few cross links are introduced in the chain.

6. Biopolymers: Polysaccharides (starch, cellulose), protein and nucleic acid are called biopolymers and it is an example of natural polymer.

Introduction for natural polymers

Polymers are macromolecules (giant molecules of higher molecular weight) formed by the repeated linking of large number of small molecules called monomers. The polymers obtained from nature (plants and animals) are called natural polymers. Natural polymer is one of the types of polymers. These natural polymers are found in plants and animals. Examples for natural polymer are proteins, cellulose, starch, resin and natural rubber.

Types of Natural Polymer

Polymers may be classified in more than one manner. The conventional classification is denoted in following

Polymer:

1. Natural polymers

Organic

· Cellulose

· RNA and DNA

· Proteins

· Polypeptides

Inorganic

· Clay (silicates)

· Synthetic polymers

Organic

· Polyethylene

· Polypropylene

· Polyesters

· Polyurethanes

· Polyvinyl

Inorganic

· Silicones.

Natural Polymers :

a) Collagen

• b) AlbuminNatural polymers remains the primary choice of formulator because

- They are natural products of living organism

- Readily available

- Relatively inexpensive

- Capable of chemical modification

• Moreover, it satisfies most of the ideal requirements of polymers.

• But the only and major difficulty is the batch- to-batch reproducibility and purity of the sample.

c) Casein

d) gelatin

• Examples :

1) Proteins :

- Collagen : Found from animal tissue.

Used in absorbable sutures, sponge wound dressing, as drug delivery vehicles

- Albumin : Obtained by fabrication of blood from healthy donor.

Used as carriers in nanocapsules & microspheres

- Gelatin : A natural water soluble polymer

Used in capsule shells and also as coating material in microencapsulation

2) Polysaccharides :

- Starch :

Usually derivatised by introducing acrylic groups before manufactured into microspheres.

Also used as binders.

- Cellulose :

Naturally occuring linear polysaccharide. It is insoluble in water but solubility can be obtained by substituting -OH group.

Na-CMC is used as thickner, suspending agent, and film formers.

3) DNA &RNA :

They are the structural unit of our body. DNA is the blueprint that determines everything of our body.

pharmacology mnemonics for easy memorizing

2010-11-13T11:49:00.000-08:00

PHARMACOLOGY

Hepatic necrosis: drugs causing focal to massive necrosis 409]

"Very Angry Hepatocytes":

Valproic acid

Acetaminophen

Halothane

Adrenoceptors: vasomotor function of alpha vs. beta 2144]

ABCD:

Alpha = Constrict.

Beta = Dilate.

Antiarrhythmics: class III members 2043]

BIAS:

Bretylium

Ibutilide

Amiodarone

Sotalol

Beta blockers with intrinsic sympathomimetic activity 1534]

Picture diabetic and asthmatic kids riding away on a cart that rolls on pinwheels.

Pindolol and Carteolol have high and moderate ISA respectively, making them acceptable for use in some

diabetics or asthmatics despite the fact that they are non-seletive beta blockers.

David Shprecher Lake Erie College of Osteopathic Medicine

Beta-blockers: main contraindications, cautions 518]

ABCDE:

Asthma

Block (heart block)

COPD

Diabetes mellitus

Electrolyte (hyperkalemia)

Anonymous Contributor

Beta-blockers: nonselective beta-blockers 1725]

"Tim Pinches His Nasal Problem" (because he has a runny nose...):

Timolol

Pindolol

Hismolol

Naldolol

Propranolol

Captopril (an ACE inhibitor): side effects 515]

CAPTOPRIL:

Cough

Angioedema/ Agranulocystosis

Proteinuria/ Potassium excess

Taste changes

Orthostatic hypotension

Pregnancy contraindication/ Pancreatitis/ Pressure drop (first dose hypertension)

Renal failure (and renal artery stenosis contraindication)/ Rash

Indomethacin inhibition

Leukopenia/ Liver toxicity

Enoxaprin (prototype low molecular weight heparin): action, monitoring 1657]

EnoXaprin only acts on factor Xa.

Monitor Xa concentration, rather than APTT.

HMG-CoA reductase inhibitors (statins): side effects, contraindications, interactions 2025]

HMG-CoA:

_ Side effects:

Hepatotoxicity

Myositis [aka rhabdomyolysis]

_ Contraindications:

Girl during pregnancy/ Growing children

_ Interactions:

Coumarin/ Cyclosporine

Hypertension: treatment 2627]

ABCD:

ACE inhibitors/ AngII antagonists (sometimes Alpha agonists also)

Beta blockers

Calcium antagonists

Diuretics

Patent ductus arteriosus: treatment 1191]

"Come In and Close the door":

INdomethacin is used to Close PDA.

Milixa Fortuna UAG Medical Student

Propranolol and related '-olol' drugs: usage 246]

"olol" is just two backwards lower case b's.

Backward b's stand for "beta blocker".

_ Beta blockers include acebutolol, betaxolol, bisoprolol, oxprenolol, propranolol.

Thrombolytic agents 1902]

USA:

Urokinase

Streptokinase

Alteplase (tPA)

Warfarin: action, monitoring 432]

WePT:

Warfarin works on the extrinsic pathway and is monitored by PT.

Warfarin: metabolism 901]

SLOW:

_ Has a slow onset of action.

_ A quicK Vitamin K antagonist, though.

Small lipid-soluble molecule

Liver: site of action

Oral route of administration.

Warfarin

Gynaecomastia-causing drugs 1798]

DISCOS:

Digoxin

Isoniazid

Spironolactone

Cimetidine

Oestrogens

Stilboestrol

K+ increasing agents 2088]

K-BANK:

K-sparing diuretic

Beta blocker

ACEI

NSAID

K supplement

Propythiouracil (PTU): mechanism 1617]

It inhibits PTU:

Peroxidase/ Peripheral deiodination

Tyrosine iodination

Union (coupling)

Steroid side effects 1526]

CUSHINGOID:

Cataracts

Ulcers

Skin: striae, thinning, bruising

Hypertension/ Hirsutism/ Hyperglycemia

Infections

Necrosis, avascular necrosis of the femoral head

Glycosuria

Osteoporosis, obesity

Immunosuppression

Diabetes

Steroids: side effects 483]

BECLOMETHASONE:

Buffalo hump

Easy bruising

Cataracts

Larger appetite

Obesity

Moonface

Euphoria

Thin arms & legs

Hypertension/ Hyperglycaemia

Avascular necrosis of femoral head

Skin thinning

Osteoporosis

Negative nitrogen balance

Emotional liability

Lupus: drugs inducing it 530]

HIP:

Hydralazine

INH

Procanimide

Diuretics: thiazides: indications 2091]

"CHIC to use thiazides":

CHF

Hypertension

Insipidous

Calcium calculi

Nitrofurantoin: major side effects 482]

NitroFurAntoin:

Neuropathy (peripheral neuropathy)

Fibrosis (pulmonary fibrosis)

Anemia (hemolytic anemia)

Osmotic diuretics: members 772]

GUM:

Glycerol

Urea

Mannitol

SIADH-inducing drugs 2086]

ABCD:

Analgesics: opioids, NSAIDs

Barbiturates

Cyclophosphamide/ Chlorpromazine/ Carbamazepine

Diuretic (thiazide)

Sulfonamide: major side effects 774]

_ Sulfonamide side effects:

Steven-Johnson syndrome

Skin rash

Solubility low (causes crystalluria)

Serum albumin displaced (causes newborn kernicterus and potentiation of other serum albumin-binders like warfarin)

Vir-named drugs: use 771]

"-vir at start, middle or end means for virus":

_ Drugs: Abacavir, Acyclovir, Amprenavir, Cidofovir, Denavir, Efavirenz, Indavir, Invirase, Famvir, Ganciclovir, Norvir, Oseltamivir,

Penciclovir, Ritonavir, Saquinavir, Valacyclovir, Viracept, Viramune, Zanamivir, Zovirax.

4-Aminopyradine (4-AP) use 768]

"4-AP is For AP":

For AP (action potential) propagation in Multiple Sclerosis.

Anticholinergic side effects 1958]

"Know the ABCD'S of anticholinergic side effects":

Anorexia

Blurry vision

Constipation/ Confusion

Dry Mouth

Sedation/ Stasis of urine

Antimuscarinics: members, action 1187]

"Inhibits Parasympathetic And Sweat":

Ipratropium

Pirenzepine

Atropine

Scopolamine

_ Muscarinic receptors at all parasympathetic endings sweat glands in sympathetic.

Aspirin: side effects 1349]

ASPIRIN:

Asthma

Salicyalism

Peptic ulcer disease/ Phosphorylation-oxidation uncoupling/ PPH/ Platelet disaggregation/ Premature closure of PDA

Intestinal blood loss

Reye's syndrome

Idiosyncracy

Noise (tinnitus)

Benzodiazapines: ones not metabolized by the liver (safe to use in liver failure) 1566]

LOT:

Lorazepam

Oxazepam

Temazepam

Benzodiazepenes: antidote 776]

"Ben is off with the flu":

Benzodiazepine effects off with Flumazenil.

Benzodiazepenes: drugs which decrease their metabolism 875]

"I'm Overly Calm":

Isoniazid

Oral contraceptive pills

Cimetidine

_ These drugs increase calming effect of BZDs by retarding metabolism.

Benzodiazepines: actions 464]

"Ben SCAMs Pam into seduction not by brain but by muscle":

Sedation

anti-Convulsant

anti-Anxiety

Muscle relaxant

Not by brain: No antipsychotic activity.

Beta 1 selective blockers 2148]

"BEAM ONE up, Scotty":

Beta 1 blockers:

Esmolol

Atenolol

Metropolol

Botulism toxin: action, related bungarotoxin 229]

Action: "Botulism Bottles up the Ach so it can't be the released":

Related bungarotoxin: "Botulism is related to Beta Bungarotoxin (beta-, not alpha-bungarotoxin--alpha has different mechanism).

Cholinergics (eg organophosphates): effects 388]

If you know these, you will be "LESS DUMB":

Lacrimation

Excitation of nicotinic synapses

Salivation

Sweating

Diarrhea

Urination

Micturition

Bronchoconstriction

Delerium-causing drugs 617]

ACUTE CHANGE IN MS:

Antibiotics (biaxin, penicillin, ciprofloxacin)

Cardiac drugs (digoxin, lidocaine)

Urinary incontinence drugs (anticholinergics)

Theophylline

Ethanol

Corticosteroids

H2 blockers

Antiparkinsonian drugs

Narcotics (esp. mepridine)

Geriatric psychiatric drugs

ENT drugs

Insomnia drugs

NSAIDs (eg indomethacin, naproxin)

Muscle relaxants

Seizure medicines

Direct sympathomimetic catecholamines 769]

DINED:

Dopamine

Isoproterenol

Norepinephrine

Epinephrine

Dobutamine

Inhalation anesthetics 534]

SHINE:

Sevoflurane

Halothane

Isoflurane

Nitrous oxide

Enflurane

_ If want the defunct Methoxyflurane too, make it MoonSHINE.

Ipratropium: action 231]

Atropine is buried in the middle: iprAtropium, so it behaves like Atropine.

Lead poisoning: presentation 517]

ABCDEFG:

Anemia

Basophilic stripping

Colicky pain

Diarrhea

Encephalopathy

Foot drop

Gum (lead line)

Lithium: side effects 531]

LITH:

Leukocytosis

Insipidus [diabetes insipidus, tied to polyuria]

Tremor/ Teratogenesis

Hypothyroidism

MAOIs: indications 2059]

MAOI'S:

Melancholic [classic name for atypical depression]

Anxiety

Obesity disorders [anorexia, bulemia]

Imagined illnesses [hypochondria]

Social phobias

_ Listed in decreasing order of importance.

_ Note MAOI is inside MelAnchOlIc.

Methyldopa: side effects 487]

METHYLDOPA:

Mental retardation

Electrolyte imbalance

Tolerance

Headache/ Hepatotoxicity

psYcological upset

Lactation in female

Dry mouth

Oedema

Parkinsonism

Anaemia (haemolytic)

Monoamine oxidase inhibitors: members 1186]

"PIT of despair":

Phenelzine

Isocarboxazid

Tranylcypromine

_ A pit of despair, since MAOs treat depression.

Morphine: effects 1174]

MORPHINES:

Miosis

Orthostatic hypotension

Respiratory depression

Pain supression

Histamine release/ Hormonal alterations

Increased ICT

Nausea

Euphoria

Sedation

Morphine: effects at mu receptor 1837]

PEAR:

Physical dependence

Euphoria

Analgesia

Respiratory depression

Narcotic antagonists 533]

The Narcotic Antagonists are NAloxone and NAltrexone.

_ Important clinically to treat narcotic overdose.

Parkinsonism: drugs 1812]

SALAD:

Selegiline

Anticholinenergics (trihexyphenidyl, benzhexol, ophenadrine)

L-Dopa + peripheral decarboxylase inhibitor (carbidopa, benserazide)

Amantadine

Dopamine postsynaptic receptor agonists (bromocriptine, lisuride, pergolide)

Phenytoin: adverse effects 1796]

PHENYTOIN:

P-450 interactions

Hirsutism

Enlarged gums

Nystagmus

Yellow-browning of skin

Teratogenicity

Osteomalacia

Interference with B12 metabolism (hence anemia)

Neuropathies: vertigo, ataxia, headache

Physostigmine vs. neostigmine 1434]

LMNOP:

Lipid soluble

Miotic

Natural

Orally absorbed well

Physostigmine

_ Neostigmine, on the contrary, is:

Water soluble

Used in myesthenia gravis

Synthetic

Poor oral absorption

Pupils in overdose: morphine vs. amphetamine 156]

"MorPHINE: Fine. AmPHETamine: Fat":

Morphine overdose: pupils constricted (fine).

Amphetamine overdose: pupils dilated (fat).

Serotonin syndrome: components 2273]

Causes HARM:

Hyperthermia

Autonomic instability (delirium)

Rigidity

Myoclonus

Sodium valproate: side effects 493]

VALPROATE:

Vomiting

Alopecia

Liver toxicity

Pancreatitis/ Pancytopenia

Retention of fats (weight gain)

Oedema (peripheral oedema)

Appetite increase

Tremor

Enzyme inducer (liver)

SSRIs: side effects 532]

SSRI:

Serotonin syndrome

Stimulate CNS

Reproductive disfunctions in male

Insomnia

Succinylcholine: action, use 248]

Succinylcholine gets Stuck to Ach receptor, then Sucks ions in through open pore.

You Suck stuff in through a mouth-tube, and drug is used for intubation.

Tricyclic antidepressants: members worth knowing 2236]

"I have to hide, the CIA is after me":

Clomipramine

Imipramine

Amitrptyline

_ If want the next 3 worth knowing, the DNDis also after me:

Desipramine

Norrtriptyline

Doxepin

Tricyclic antidipressents (TCA): side effects 2878]

TCA'S:

Thrombocytopenia

Cardiac (arrhymia, MI, stroke)

Anticholinergic (tachycardia, urinary retention, etc)

Seizures

Vigabatrin: mechanism 1578]

Vi-GABA-Tr-In:

Via GABA Transferase Inhibition

Antibiotics contraindicated during pregnancy 1250]

MCAT:

Metronidazole

Chloramphenicol

Aminoglycoside

Tetracycline

Busulfan: features 2198]

ABCDEF:

Alkylating agent

Bone marrow suppression s/e

CML indication

Dark skin (hyperpigmentation) s/e

Endrocrine insufficiency (adrenal) s/e

Fibrosis (pulmonary) s/e

Cancer drugs: time of action between DNA->mRNA 2195]

ABCDEF:

Alkylating agents

Bleomycin

Cisplastin

Dactinomycin/ Doxorubicin

Etoposide

Flutamide and other steroids or their antagonists (eg tamoxifen, leuprolide)

Etoposide: action, indications, side effect 1193]

"eTOPoside":

_ Action:

Inhibits TOPoisomerase II

_ Indications:

Testicular carcinoma

Oat cell carcinoma of lung

Prostate carcinoma

_ Side effect:

Affects TOP of your head, causing alopecia

Metabolism enzyme inducers 299]

"Randy's Black Car Goes Putt Putt and Smokes":

Rifampin

Barbiturates

Carbamazepine

Grisoefulvin

Phenytoin

Phenobarb

Smoking cigarettes

Morphine: side-effects 2550]

MORPHINE:

Myosis

Out of it (sedation)

Respiratory depression

Pneumonia (aspiration)

Hypotension

Infrequency (constipation, urinary retention)

Nausea

Emesis

Therapeutic index: formula 2032]

TILE:

TI = LD50 / ED50

Torsades de Pointes: drugs causing 2269]

APACHE:

Amiodarone

Procainamide

Arsenium

Cisapride

Haloperidol

Eritromycin

Zero order kinetics drugs (most common ones) 462]

"PEAZ (sounds like pees) out a constant amount":

Phenytoin

Ethanol

Aspirin

Zero order

_ Someone that pees out a constant amount describes zero order kinetics (always the same amount out)

Asthma drugs: leukotriene inhibitor action 2241]

zAfirlukast: Antagonist of lipoxygenase

zIlueton: Inhibitor of LT receptor

Beta-1 vs Beta-2 receptor location 34]

"You have 1 heart and 2 lungs":

Beta-1 are therefore primarily on heart.

Beta-2 primarily on lungs.

Respiratory depression inducing drugs 1980]

"STOP breathing":

Sedatives and hypnotics

Trimethoprim

Opiates

Polymyxins

Ribavirin: indications 2101]

RIBAvirin:

RSV

Influenza B

Arenaviruses (Lassa, Bolivian, etc.)

TB: antibiotics used 1581]

STRIPE:

STreptomycin

Rifampicin

Isoniazid

Pyrizinamide

Ethambutol

Zafirlukast, Montelukast, Cinalukast: mechanism, usage 648]

"Zafir-luk-ast, Monte-luk-ast, Cina-luk-ast":

_ Anti-Lukotrienes for Asthma.

_ Dazzle your oral examiner: Zafirlukast antagonizes leukotriene-4.

Teratogenic drugs: major non-antibiotics 1433]

TAP CAP:

Thalidomide

Androgens

Progestins

Corticosteroids

Aspirin & indomethacin

Phenytoin

Tetracycline: teratogenicity 876]

TEtracycline is a

TEratogen that causes staining of

TEeth in the newborn.

Antirheumatic agents (disease modifying): members 2035]

CHAMP:

Cyclophosphamide

Hydroxycloroquine and choloroquinine

Auranofin and other gold compounds

Methotrexate

Penicillamine

Auranofin, aurothioglucose: category and indication 2036]

Aurum is latin for "gold" (gold's chemical symbol is Au).

Generic Aur- drugs (Auranofin, Aurothioglucose) are gold compounds.

_ If didn't learn yet that gold's indication is rheumatoid arthritis, AUR- Acts Upon Rheumatoid.

emergency drugs pneumonics

2010-11-13T11:22:00.000-08:00

Activated charcoal: contraindications

CHEMICAL CamP:
Cyanide
Hydrocarbons
Ethanol
Metals
Iron
Caustics
Airway unprotected
Lithium
CAMphor
Potassium
Show Details / Rate It
---Vince Yamashiroya

Ipecac: contraindications

4 C's:
Comatose
Convulsing
Corrosive
hydroCarbon
Show Details / Rate It

Vfib/Vtach drugs used according to ACLS

"Every Little Boy Must Pray":
Epinephrine
Lidocaine
Bretylium
Magsulfate
Procainamide
Show Details / Rate It
---Midnight Medic Paramedic in Texas

Shock: signs and symptoms

TV SPARC CUBE:
Thirst
Vomiting
Sweating
Pulse weak
Anxious
Respirations shallow/rapid
Cool
Cyanotic
Unconscious
BP low
Eyes blank
Show Details / Rate It
---Anonymous Contributor

Acute LVF management

LMNOP:
Lasex (frusemide)
Morphine (diamorphine)
Nitrates
Oxygen (sit patient up)
Pulmonary ventilation (if doing badly)
Show Details / Rate It
---Graeme Little University College London

Subarachnoid hemorrhage (SAH) causes

BATS:
Berry aneurysm
Arteriovenous malformation/ Adult polycystic kidney disease
Trauma (eg being struck with baseball bat)
Stroke
Show Details / Rate It
---Cusano and Mamta SGUSOM

Ventricular fibrillation: treatment

"Shock, Shock, Shock, Everybody Shock, Little Shock, Big Shock, Momma Shock, Poppa Shock":
Shock= Defibrillate
Everybody= Epinephine
Little= Lidocaine
Big= Bretylium
Momma= MgSO4
Poppa= Pocainamide
Show Details / Rate It
---Anonymous Contributor

Chest pain treatment, for nurses

"MOVE your patient!":
Monitor: put patient on cardiac monitor
Oxygen: put patient on O2
Venous: gain large bore venous access
EKG: 12 lead EKG
Show Details / Rate It
---R. Stilts, S.N. Senior Nursing Student

Endotrachial tube deliverable drugs

O NAVEL:
Oxygen
Naloxone
Atropine
Ventolin (albuterol)
Epinephrine
Lidocaine
· If you can't get IV access established, and have necessity to administer resuscitative meds, remember you have the airway and can give the above drugs.
· Drug delivery is enhanced if diluted with 10cc NS and rapid introduced for aeresolization.
· Alternatively, bare bone version is ALE, as above.
Show Details / Rate It
---Robert Lueken and Marc Eastern Virginia Medical School

Syncope causes, by system

HEAD HEART VESSELS:
· CNS causes include HEAD:
Hypoxia/ Hypoglycemia
Epilepsy
Anxiety
Dysfunctional brain stem (basivertebral TIA)
· Cardiac causes are HEART:
Heart attack
Embolism (PE)
Aortic obstruction (IHSS, AS or myxoma)
Rhythm disturbance, ventricular
Tachycardia
· Vascular causes are VESSELS:
Vasovagal
Ectopic (reminds one of hypovolemia)
Situational
Subclavian steal
ENT (glossopharyngeal neuralgia)
Low systemic vascular resistance (Addison's, diabetic vascular neuropathy)
Sensitive carotid sinus
Show Details / Rate It
---Bill Young MD University of Kentucky Dept of Emergency Medicine

Atrial fibrillation: causes of new onset

THE ATRIAL FIBS:
Thyroid
Hypothermia
Embolism (P.E.)
Alcohol
Trauma (cardiac contusion)
Recent surgery (post CABG)
Ischemia
Atrial enlargement
Lone or idiopathic
Fever, anemia, high-output states
Infarct
Bad valves (mitral stenosis)
Stimulants (cocaine, theo, amphet, caffeine)
Show Details / Rate It
---Sam LaCapra, M.D., F.A.C.E.P. Emergency Physician

Malaria: complications of falciparum malaria

CHAPLIN:
Cerebral malaria/ Coma
Hypoglycemia
Anaemia
Pulmonary edema
Lactic acidosis
Infections
Necrois of renal tubules (ATN)
Show Details / Rate It
---Dr. Harsh Sharma BJMC, Pune, India

MI: immediate treatment

DOGASH:
Diamorphine
Oxygen
GTN spray
Asprin 300mg
Streptokinase
Heparin
Show Details / Rate It
---Ken Hodson Medical Student, University of Bristol

Pain history checklist

OLDER SAAB:
Onset
Location
Description (what does it feel like)
Exacerbating factors
Radiation
Severity
Associated symptoms
Alleviating factors
Before (ever experience this before)
Show Details / Rate It
---Lissa Bird, NREMT-P

Pulseless Electrical Activity (PEA): checklist

PEA:
Pulses check
Epinepherine
Atropine
Show Details / Rate It
---Anonymous Contributor

PEA/Asystole (ACLS): etiology

ITCHPAD:
Infarction
Tension pneumothorax
Cardiac tamponade
Hypovolemia/ Hypothermia/ Hypo-, Hyperkalemia/ Hypomagnesmia/ Hypoxemia
Pulmonary embolism
Acidosis
Drug overdose
Show Details / Rate It
---Carl Roberts A.S.EMS, CCEMT-P, CFP US Army Special Forces

V-fib/pulseless v-tach (new ACLS as of 2001)

"EVAL My Pumper":
Epinephrine
Vasopressin
Amiodarone (class IIb--better for heart failure)
Lidocaine (indeterminate - better for young, healthy or persistent)
MgSO4 (IIb for hypomagnesemic state or torsades)
Procainamide (IIb for intermittent/recurrent VF/VT)
Show Details / Rate It
---Brenda L. Snyder, RN, CEN, PHRN George Washington University Hospital, Washington, D.C.

Asystole: treatment

"Have some asystole "TEA":
Transcutaneous pacing
Epi
Atropine
Show Details / Rate It
---Brenda L. Snyder, RN, CEN, PHRN George Washington University Hospital, Washington, D.C.

JVP: raised JVP differential

PQRST (EKG waves):
Pericardial effusion
Quantity of fluid raised (fluid over load)
Right heart failure
Superior vena caval obstruction
Tricuspid stenosis/ Tricuspid regurgitation/ Tamponade (cardiac)
Show Details / Rate It
---Dr. Mohsin Maqbool Bahawal-Victoria Hospital, Bahawalpur

JVP: raised JVP: extra-cardiac causes

FAT PEA:
Fever
Anaemia
Thyrotoxicosis
Pregnancy
Exercise
A-V fistula
· These are in addition to all the cardiac ones (pericardial effusion, RHF, tricuspid stenosis, SVC obstruction, etc).
Show Details / Rate It
---Rajeev Peravali Year 3 Medical student, Birmingham University, UK

Shock: general features

CHORD ITEM:
Cold, clammy skin
Hypotension
Oliguria
Rapid, shallow breathing
Drowsiness, confusion
Irritability
Tachycardia
Elevated or reduced central venous pressure
Multi-organ damage
Show Details / Rate It
---Seyi Kayode College of Health Sciences, Obafemi Awolowo University, Ile-ife, Osun State, Nigeria

Myocardial infarction: some emergency treatment drugs

ABCD:
Aspirin
Beta blockers
Clot busters (thromboytics)
Dynamite (nitrates)
Show Details / Rate It
---Ray Gadd Student, Australia

Snakebite scoring system

· 6 T's:
Toothless
T-shirt
Tattooed
Trailer park
Testosterone
Tequila (EtOH)
· One point for each positive.
· 3 or more positive T's suggests venomous bite.
Show Details / Rate It

Coma causes checklist

AEIOU TIPS:
Acidosis/ Alcohol
Epilepsy
Infection
Overdosed
Uremia
Trauma to head
Insulin: too little or or too much
Pyschosis episode
Stroke occurred
Show Details / Rate It
---Midnight Medic Paramedic in Texas

Unconciousness: differential

FISH SHAPED:
Fainted
Illness/ Infantile febrile convulsions
Shock
Head injuries
Stroke (CVE)
Heart problems
Asphxia
Poisons
Epilepsy
Diabetes
Show Details / Rate It
---B Sylvester Surrey Ambulance Service (UK)

Organophosphates poisoning symptoms

MILES:
Miosis
Increased urinary frequency
Lacrimation
Enuresis
Salivation
Show Details / Rate It
---Anonymous Contributor

ICU confusion causes

ICU CONFUSION:
ICU psychosis
Cardiac output low [hypotension, post cardiac arrest]
Uncontrolled temperature [hypo/hyperthermia]
Convulsion [post ictal]
Oxygen [hypoxia, hypercarbia]
Nociception [pain]
Full bladder
Uremia
Sugar [hypo/hyperglycemia]
Infection
Opiates
Natremia [hypo/hyper]
Show Details / Rate It
---Dr. Sonali Vadi

Neurological focal deficits

10 S's:
Sugar (hypo, hyper)
Stroke
Seizure (Todd's paralysis)
Subdural hematoma
Subarachnoid hemorrhage
Space occupying lesion (tumor, avm, aneurysm, abscess)
Spinal cord syndromes
Somatoform (conversion reaction)
Sclerosis (MS)
Some migraines
Show Details / Rate It
---Sam LaCapra, M.D., F.A.C.E.P. Emergency Physician

Miosis: causes of pin-point pupils

CPR ON SLIME:
Clonidine
Phenothiazines
Resting (deep sleep)
Opiates
Narcotics
Stroke (pontine hemorrhage)
Lomotil (diphenoxylate)
Insecticides
Mushrooms/ Muscarinic (inocybe, clitocybe)
Eye drops
Show Details / Rate It
---Sam LaCapra, M.D., F.A.C.E.P. Emergency Physician

Meningicoccal meningitis: complications

SAD REP:
Sepsis/ Shock/ Subdural effusion
Ataxia/ Abscess (brain)
DIC/ Deafness
Retardation
Epilepsy
Paralysis
Show Details / Rate It
---Richard Thompson Queens University, Belfast, NI

Organophosphates poisoning: symptoms

DUMBBELS:
Diarrhea
Urination
Miosis
Bradycardia
Bronchospasm
Emesis
Lacrimation
Salivation
Show Details / Rate It
---Martin Herman Le Bonheur Children's Medical Center

Coma: differential

UNCONSCIOUS:
Units of insulin
Narcotics
Convulsions
Oxygen
Nonorganic
Stroke
Cocktail
ICP
Organism
Urea
Shock
Show Details / Rate It
---Tom Hiser Clear Lake Emergency Medical Corps

Seizures: differential

SICK DRIFTER:
Substrates (sugar, oxygen)
Isoniazid overdose
Cations (Na, Ca, Mg)
Kids (ecclampsia)
Drugs (CRAP: Cocaine, Rum (alcohol), Amphetamines, PCP)
Rum (alchohol withdrawl)
Illnesses (chronic seizure disorder or other chronic disorder)
Fever (meningitis, encephalitis, abscess)
Trauma (epidural, subdural, intraparynchymal hemorrhage)
Extra: toxocologic (TAIL: Theo, ASA, Isoniazid, Lithium) and 3 Anti's: (Antihistamine overdose, Antidepressant overdose, Anticonvulsants (too high dilanitin, tegretol) or benzo withdrawl.
Rat poison (organophospates poisoning)
Show Details / Rate It
---Joseph Rogers, MD Duke University

Seizure: quick history taking

FACT:
Focus: generalized vs. local activity
Activity: tonic-clonic vs. absence
Color: red, blue, ashen--possible indicator of hypoxia
Time: length of seizure
Show Details / Rate It
---James Lovell, BS, RN, EMT-P LifeAid

Fits: causes

HOWARD:
Hypertension
Obesity
Warfarin
Alcohol
Retardation
Drugs

Coma: conditions to exclude as cause MIDAS:
Meningitis
Intoxication
Diabetes
Air (respiratory failure)
Subdural/ Subarachnoid hemorrhage
Show Details / Rate It
---Anonymous Contributor
Resuscitation: basic steps ABCDE:
Airway
Breathing
Circulation
Drugs
Environment
Show Details / Rate It
---Mohamed Azim, MD Pediatric Surgeon, Alexandria University, Egypt
Malignant hyperthermia treatment "Some Hot Dude Better Give Iced Fluids Fast!" (Hot dude = hypothermia):
Stop triggering agents
Hyperventilate/ Hundred percent oxygen
Dantrolene (2.5mg/kg)
Bicarbonate
Glucose and insulin
IV Fluids and cooling blanket
Fluid output monitoring/ Furosemide/ Fast heart [tachycardia]
Show Details / Rate It
---Anonymous Contributor
Shock: types RN CHAMPS:
Respiratory
Neurogenic
Cardiogenic
Hemorrhagic
Anaphylactic
Metabolic
Psychogenic
Septic
· Alternatively: "MR. C.H. SNAP", or "NH CRAMPS".
Show Details / Rate It
---Anonymous Contributor
Chest pain: differential CHEST PAIN:
Costochondritis/ Cocaine abuse
Herpes zoster/ Hyperventilation
Esophagitis/ Esophageal spasm
Stenosis (AS)
Trauma
PE/ Pneumonia/ Pneumothorax/ Pericarditis/ Pancreatitis
Angina/ Aortic dissection/ Aortic anerusym
Infarction/ IV disk disease
Neuropsychiatric disorders (e.g. depression, Da Costa's)
Show Details / Rate It
---Fahed Al-Daour
RLQ pain: differential APPENDICITIS:
Appendicitis/ Abscess
PID/ Period
Pancreatitis
Ectopic/ Endometriosis
Neoplasia
Diverticulitis
Intussusception
Crohns Disease/ Cyst (ovarian)
IBD
Torsion (ovary)
Irritable Bowel Syndrome
Stones
Show Details / Rate It
---Anonymous Contributor
Coma and signicantly reduced conscious state causes: causes COMA:
CO2 and CO excess
Overdose: TCAs, Benzos, EtOH, insulin, paracetamol, etc.
Metabolic: BSL, Na+, K+, Mg2+, urea, ammonia, etc.
Apoplexy: stroke, SAH, extradural, subdural, Ca, meningitis, encephalitis, cerebral abscess, etc.
Show Details / Rate It
---Steve Gust HMO, Gove District Hospital, NT Australia
Trauma: motor vehicle accident considerations I AM SCARED:
Impact (head-on, rear-end, t-bone, rollover, rotational etc.)
Auto vs. pedestrian, bike, motorcycle (start @ speed >10mph)
Medical history (cardiac, coagulolation, liver, immuno, obese, prego)
Speed (>50 mph?)
Compartment intrusion (>12 inches?)
Age (<5>55 y.o.?)
Restraints (lap & shoulder, either, airbag, infant or child seat?)
Ejection/ Extrication (eject=25x greater death, extr>20min)
Death (at scene, same vehicle, other)
Show Details / Rate It
---Brenda L. Snyder, RN, CEN, PHRN George Washington University Hospital, Washington, D.C.
Kendrick Extrication Device (K.E.D.): order of placing straps "My Baby Looks Hot Tonight":
Middle
Bottom
Legs
Head
Top
· Note: K.E.D. is a device used to extract patients out of a crashed car or similar tight space.
Show Details / Rate It
---Anonymous Contributor
Blackout/collapse: causes THE VESPA MC:
TIA
Hypoglycemia
Epilepsy
Vasovagal
Epilepsy
Situation
Ppostural hypotension/ PE
Arrthymia/ Aortic stenosis(HOCM)
Myocardial infarction
Carotid sinus hypersensitivity
Show Details / Rate It
---Jude McSharry University College Hospital Galway

Motor Vehicle Collision (MVC): Single vehicle MVC differential of causes

· 7 S's:
Suds (EtOH)
Suicide
Sleep
Seizure
Sugar
Stroke (bleed)
Stupidity

Decompression sickness

Boyle's law: volume of gas is inversely proportionate to its pressure.
· Therefore, BOYLE:
Breathe (as you ascend)
Or
Your
Lung
Explodes
· Breathe as you ascend after scuba diving, since the pressure decreases on surfacing, so the gas volume in lungs increases.

Show Details / Rate It
---Mohamed Azim, MD Assistant lecturer, Pediatric surgery, Alexandria University, Egypt

Endotracheal tube: troubleshooting

DOPEY:
Displaced: esophagus, right mainstem, back of throat, etc
Obstructed: secretions, blood, mucus plug, kink, etc
Pneumothorax
Equipment: malfunctions, O2, ETT, BVM, ventilator, monitor
You: your approach, technique: missing something?
Show Details / Rate It
---Brenda L. Snyder, RN, CEN, PHRN George Washington University Hospital, Washington, D.C.

ARDS: diagnostic criteria

ARDS:
Acute onset
Ratio (PaO2/FiO2) less than 200
Diffuse infiltration
Swan-Ganz Wedge pressure less than 19 mmHg
Show Details / Rate It
---Fahed Al-Daour

ARDS: full differential

CARDS? HOPE ITS NOT ARDS:
CNS disorders
Aspiration (gastric)
Radiation
Drugs (heroin, morphine, barbiturates, etc)
Smoke, toxic gas inhalation
Hypotension, shock
Oxygen toxicity
Pancreatitis
Emboli
Infection, sepsis
Transfusion reaction
Surgery (esp. cardiac)
Near drowning
Obstetrical emergencies (eg eclampsia, HELLP)
Thermal injuries/ burns
Altitude sickness
Renal failure
DIC
SLE
Show Details / Rate It
---Fahed Al-Daour

Pneumothorax: causes

SIT, 3 A's, 3 C's:
Spontaneous (often tall thin men)
Iatrogenic
Trauma
Asthma
Alveolitis
AIDS
COPD
Carcinoma
Cystic fibrosis
Show Details / Rate It
---Jamal Khan Birmingham University Medical Student

Shortness of breath: short differential

AAAA PPPP:
Airway obstruction
Angina
Anxiety
Asthma
Pneumonia
Pneumothorax
Pulmonary Edema
Pulmonary Embolus
Show Details / Rate It
---Anonymous Contributor

Dyspnea: differential

3A's: Three Airways: Airway obstruction, Anaphylaxis, Asthma
3P's: Three Pulmonary's: Pneumothorax, PE, Pulmonary edema
3C's: Three Cardiacs: Cardiogenic pulmonary edema, Cardiac ischemia, Cardiac tamponade
3M's: Three Metabolics: (DOC) DKA, Organophosphates, Carbon monoxide poisoning
Show Details / Rate It
---Joseph Rogers, MD Duke University

Pneumonia: hospitalisation criteria

ABCD:
Age greater than 60
Blood urea greater than 7 mmol/l
Confusion
Diastolic BP less than 60 mmHg
·Hospitalise the pneumonia patient if 2 or more of these criteria are met.
Show Details / Rate It
---Fahed Al-Daour Medical Student

Asthma acute attack: 5 life threatening signs

SHOCK:
Silent chest
Hypotension
One third of best/predicted PFR
Cyanosis
Konfusion
Show Details / Rate It
---Anonymous Contributor

Fall: potential causes CLADE SPADE:
Cardiovascular/ Cerebrovascular
Locomotor (skeletal, muscular, neurological)
Ageing (increased body sway, decreased reaction time)
Drugs (esp. antihypertensives, antipsychotics)
Environmental
Sensory deficits (eg. visual problems)
Psychological/ Psychiatric (depression)
Acute illness
Dementia
Epilepsy
Show Details / Rate It
---Harris-Davies-Tamblyn Adelaide Medical School
Fall: potential causes I'VE FALLEN:
Illness
Vestibular
Environmental
Feet/ Footwear
Alcohol and drugs
Low blood pressure
Low O2 states
Ears/ Eyes
Neuropathy
Show Details / Rate It

pharmacology pneumonic

2010-11-13T11:19:00.000-08:00

Hepatomegaly: 3 common causes, 3 rarer causes

Common are 3 C's:
Cirrhosis
Carcinoma
Cardiac failure
Rarer are 3 C's:
Cholestasis
Cysts
Cellular infiltration
Show Details / Rate It
---Anonymous Contributor and Jamal Khan Not Specified and Birmingham University Medical Student

Inflammatory Bowel Disease: which has cobblestones

Crohn's has Cobblestones on endoscopy.
Show Details / Rate It
---Anonymous Contributor

PKU findings

PKU:
Pale hair, skin
Krazy (neurological abnormalities)
Unpleasant smell
Show Details / Rate It
---Robert O'Connor and Lior Greenberg

Haemochromatosis definition, classic triad

"Iron man triathalon":
Iron man: deposition of iron in many body tissues.
· Triathalon has 3 components, which match triad:
Swimming: Skin pigmentation
Biking: Bronze diabetes
Marathon: Micronodular pigment cirrhosis
· See diagram for visual equivalent.

Show Details / Rate It
---Robert O'Connor University College Dublin

Ulcerative colitis: features

ULCERATIONS:
Ulcers
Large intestine
Carcinoma [risk]
Extraintestinal manifestations
Remnants of old ulcers [pseudopolyps]
Abscesses in crypts
Toxic megacolon [risk]
Inflamed, red, granular mucosa
Originates at rectum
Neutrophil invasion
Stools bloody
Show Details / Rate It
---Samuel Atom Baek-Kim

Peptic ulcer: associated causative factors

SHAZAM:
Smoking
Hypercalcemia
Aspirin
Zollinger-Ellison
Acidity
MEN type I
· These may work with H. pylori to promote ulceration, or may act alone.
Show Details / Rate It
---Robert O'Connor University College Dublin

Carcinoid syndrome: components

CARCinoid:
Cutaneous flushing
Asthmatic wheezing
Right sided valvular heart lesions
Cramping and diarrhea
Show Details / Rate It
---Robert O'Connor University College Dublin

Gallstones/cholecystitis: risk factors

5 F's:
Fat
Female
Family history
Fertile
Forty
Show Details / Rate It
---Saif Nasafi

Kwashiorkor: distinguishing from Marasmus

FLAME:
Fatty Liver
Anemia
Malabsorption
Edema
Show Details / Rate It
---Chris UMF Bucharest

Oral cancer risks

PATH LAB:
Plummer-vinson syndrome
Alcohol
Tobacco
Human papilloma virus
Leukoplakia
Asbestos
Bad oral hygiene

Pancreatitis: causes

PANCREATITIS:
Posterior
Alcohol
Neoplasm
Cholelithiasis
Rx (lasix, AZT)
ERCP
Abdominal surgery
Trauma
Infection (mumps)
Triglycerides elevated
Idiopathic
Scorpion bite
Show Details / Rate It
---Anonymous Contributor

Hepatocellular carcinoma: aetiology, features

ABC:
Aetiology:
Aflatoxins
Hep B
Cirrhosis
· Features:
AFP increased (classic marker)
Bile-producing (DDx from cholangiocarcinoma)
Commonest primary liver tumor
Show Details / Rate It
---Robert O'Connor University College Dublin

Pancreatitis: causes

BAD S#!T:
Biliary: gallstones, 1% of ERCP patients
Alcoholism/ Azotemia
Drugs
Scorpion bite/ Sea anenome/ SLE
Hyperlipidemia/ Hypercalcemia
Idiopathic/ Infectious (mumps, coxsackie, salmonella, ascariasis)
Tumor/ Trauma
· The drugs are: penacillamine, furosemide, thiazides, ethacrynic acid, steroids, sulfas, ace inhibitors, N-SAIDs, erythromycin, estrogen.
Show Details / Rate It
---Anonymous Contributor

IBD: extraintestinal manifestations

"Left intestine to sail the SEAS of the rest of the body":
Skin manifestations: erythema nodosum, pyoderma gangrenosum
Eye inflammation: iritis, episcleritis
Arthritis
Sclerosing cholangitis
Show Details / Rate It
---Anonymous Contributor

Achalasia: 1 possible cause, 1 treatment

aCHAlasia:
1 possible cause: CHAgas' disease
1 treatment: Ca++ CHAnnel blockers
Show Details / Rate It
---Anonymous Contributor

Colon cancer: risk factors

HULA:
Heridity/ Heriditary diseases
Ulcerative colitis
Low fibre, high fat diet
Adenomatous polyps
Show Details / Rate It
---Anonymous Contributor

Colon carcinoma: aeitiology

CRAPS:
Chronic ulcerative colitis
Ratio of animal fat:fibre diet
Adenomatous polyps
Familial Polyposis
Strong family history of colon cancer.
Show Details / Rate It

Takayasu's disease is Pulseless disease

"Can't Tak'a ya pulse" (Can't take your pulse):
Takayasu's disease known as Pulseless disease, since pulse is weakened in the upper extremities.
Show Details / Rate It
---Anonymous Contributor

Acute ischemia: signs [especially limbs]

6 P's:
Pain
Pallor
Pulselessness
Paralysis
Paraesthesia
Perishingly cold
Show Details / Rate It
---Shebrain Cairo University

Hypertension: secondary hypertension causes

CHAPS:
Cushing's syndrome
Hyperaldosteronism [aka Conn's syndrome]
Aorta coarctation
Phaeochromocytoma
Stenosis of renal arteries
· Note: only 5% of hypertension cases are secondary, rest are primary.
Show Details / Rate It
---Anonymous Contributor

MI: sequence of elevated enzymes after MI

"C-AST-Le" (castle):
CK-MB first
AST second
LDH third
· Also: can use the last 'E' for ESR.
Show Details / Rate It
---Anonymous Contributor

Atherosclerosis risk factors

"You're a SAD BET with these risk factors":
Sex: male
Age: middle-aged, elderly
Diabetes mellitus
BP high: hypertension
Elevated cholesterol
Tobacco
Show Details / Rate It
---HBV Morehouse School of Medicine

Atherosclerosis risk factors

SHIFT MAID:
Smoking
Hypertension
(N)IDDM
Family history
Triglycerdides & fats
Male
Age
Inactivity
Diet / Drink
Show Details / Rate It
---Marcus McMillan Glasgow University

Thrombus: possible fates

DOPE:
Dissolution
Organization & repair
Propagation
Embolization
Show Details / Rate It
---Robert O'Connor University College Dublin

MI: sequence of elevated enzymes after MI

"Time to CALL 911":
· From first to appear to last:
Troponin
CK-MB
AST
LDH1
Show Details / Rate It
---Marco Foramiglio Centro de Ciências Médicas e Biológicas - PUC/SP- Sorocaba/SP - Brazil

Blood disorders: commoner sex

HE (male) gets:
HEmophilia (X-linked)
HEinz bodies (G6PD deficiency, causing HEmolytic anemia: X-linked)
HEmochromatosis (male predominance)
HEart attacks (male predominance)
HEnoch-Schonlein purpura (male predominance)
SHE (female) gets:
SHEehan's syndrome
Show Details / Rate It
---Anonymous Contributor

Deep venous thrombosis: genetic causes

ALASCA:
Antithrombin III
Leiden (Factor V)
APC (Activated Protein C)
S-protein deficiency
C-protein deficiency
Antiphospholipid antibody

Buerger's disease features

"burger SCRAPS":
Segmenting thrombosing vasculitis
Claudication (intermittent)
Raynaud's phenomenon
Associated with smoking
Pain, even at rest
Superficial nodular phlebitis
· Alternatively, if hungry for more detail [sic], "CRISP PIG burgers":
Chronic ulceration
Raynaud's phenomenon
Intermittent claudication
Segmenting, thrombosing vasculitis
Pain, even at rest
Phlebitis (superficial nodular)
Idiopathic
Gangrene
Show Details / Rate It
---Robert O'Connor University College Dublin

Deep venous thrombosis: diagnosis

DVT:
Dilated superficial veins/ Discoloration/ Doppler ultrasound
Venography is gold standard
Tenderness of Thigh and calf
Show Details / Rate It
---Rinku Uberoi UNIBE

Virchow's triad (venous thrombosis)

"VIRchow":
Vascular trauma
Increased coagulability
Reduced blood flow (stasis)
Show Details / Rate It
---Rinku Uberoi UNIBE

Kawasaki disease: features

Disease name: a Kawasaki motorcycle.
Usually young children, epidemic in Japan: Japanese child rides the motorcycle.
Conjunctival, oral erythema: red eyes, mouth.
Fever: thermometer.
Erythema of palms, soles: red palms, soles.
Generalized rash: rash dots.
Cervical lymphadenitis: enlarged cervical nodes with inflammation arrows.
Vasculitis of arteries: inflammation arrows on arteries.
Cardiovascular sequelae [20%]: inflammation arrows on cardiac arteries.
Treat with aspirin: aspirin headlight.
· See diagram.

Show Details / Rate It
---Robert O'Connor University College Dublin

Von Hippel-Lindau: signs and symptoms

HIPPEL:
Hemanigoblastomas
Increased renal cancer
Pheochromocytoma
Port-wine stains
Eye dysfunction
Liver, pancreas, kidney cysts
· Bare bones version: Hippel-Lindau, with H and L as above.
Show Details / Rate It
---Robert O'Connor University College Dublin

Heart failure causes

"HEART MAy DIE":
Hypertension
Embolism
Anemia
Rheumatic heart disease
Thyrotoxicosis (incl. pregnancy)
Myocardial infarct
Arrythmia
Y
Diet & lifestyle
Infection
Endocarditis
Show Details / Rate It
---The Cashman University of Queensland, Australia

Anemia causes (simplified)

ANEMIA:
Anemia of chronic disease
No folate or B12
Ethanol
Marrow failure & hemaglobinopathies
Iron deficient
Acute & chronic blood loss
Show Details / Rate It
---The Cashman University of Queensland, Australia

Pick's disease: location, action, epidemiology

· See figure.
Pick axes are Picking away at the old woman's cerebral cortex, causing cortical atrophy.
2 pick axes on her brain: frontal lobe and anterior 1/3 of temporal.
An old woman, since epidemiology is elderly & more common in women.

Show Details / Rate It
---Robert O'Connor University College Dublin

Pericarditis: findings

PERICarditis:
Pulsus paradoxus
ECG changes
Rub
Increased JVP
Chest pain [worse on inspiration, better when lean forward]
Show Details / Rate It
---Robert O'Connor University College Dublin

Fat embolism: findings

"Fat, Bat, Fract":
Fat in urine, sputum
Bat-wing lung x-ray
Fracture history
· Also, fracture of FEMur causes Fat EMboli.
Show Details / Rate It

Hemolytic anemia types

SHEEP T!T:
Sickle cell
Heriditary splenocytosis
Enzyme deficiencies: [G6P, pyruvate kinase]
Erythroblastosis fetalis
Paroxysmal nocturnal hemoglobinuria
Trauma to RBCs
Immunohemolytics: [warm Ab, cold Ag]
Thalassemias: [alpha, beta]
Show Details / Rate It
---Robert O'Connor University College Dublin

Disseminated Intravascular Cogulation: causes

DIC:
Delivery TEAR (obstetric complications)
Infections (gram negative)/ Immunological
Cancer (prostate, pancreas, lung, stomach)
· Obstretrical complications are TEAR:
Toxemia of pregnancy
Emboli (amniotic)
Abrutio placentae
Retain fetus products
Show Details / Rate It
---Khawaja Atif Farooq Rawalpindi Medical College, Islamabad, Pakistan (Gujranwala)

Thrombotic thrombocytopenic purpura: signs

FAT RN:
Fever
Anemia
Thrombocytopenia
Renal problems
Neurologic dysfunction
Show Details / Rate It
---Anonymous Contributor

Kawasaki disease: diagnostic criteria

CHILD:
5 letters=5 days, >5 years old, 5 out 6 criteria for diagnosis:
Conjuctivitis (bilateral)
Hyperthermia (fever) >5 days
Idiopathic polymorphic rash
Lymphoadenopathy (cervical)
Dryness & redness of (i)lips & month (ii)palms & soles [2 separate criteria]
Show Details / Rate It
---Wen Sun Lum University of Calgary, Canada

Protein C, Protein S: function

C and S are:
Clot
Stoppers
· These proteins inhibit coagulation.
Show Details / Rate It
---Rinku Uberoi New York Hospital

Aneurysm types

MAD SCAB:
Mycotic
Atherosclerotic
Dissecting
Syphilitic
Capillary microaneurysm
Arteriovenous fistula
Berry
Show Details / Rate It
---Sushant Varma Medical student, University of Sheffield, UK

Kawasaki's disease: features

FEAR ME:
Fever
Eye: perilimbic sparing conjunctival injection
Adenopathy: usually cervical
Rash
Mouth: red lips
Extremities: red hands and feet
· Disease to be feared because of risk of coronary aneurysms.
Show Details / Rate It
---Vince Yamashiroya

MI: complications

"LEAP on the MAP":
LVF
Embolism (systemic)
Aneurysm (ventricular)
Progressive infarction
Myocardial rupture
Arrhythmia
Pericarditis
Show Details / Rate It
---Kevin Lau University of Hong Kong

Portal hypertension: features

ABCDE:
Ascites
Bleeding (haematemesis, piles)
Caput medusae
Diminished liver
Enlarged spleen
Show Details / Rate It
---Dr. Harsh Sharma

Anemia (normocytic): causes

ABCD:
Acute blood loss
Bone marrow failure
Chronic disease
Destruction (hemolysis)
Show Details / Rate It
---Anthony Chan

TTP: clinical features

Thrombosis and thrombocytopenia PARTNER together:
Platelet count low
Anemia (microangiopathic hemolytic)
Renal failure
Temperature rise
Neurological deficits
ER admission (as it is an emergency)
Show Details / Rate It
---Anthony Chan

Macrocytic anaemia: differential

FAT RBC:
Fetus (pregnancy)
Alcohol
Thyroid disease(ie hypothyroidism)
Reticulocytosis
B12 and folate deficiency
Cirrhosis and chronic liver disease
Show Details / Rate It
---Anonymous Contributor

MI: post-MI complications

ACT RAPID:
Arrhythmias (SVT, VT, VF)
Congestive cardiac failure
Tamponade/ Thromboembolic disorders
Rupture (ventricle, septum, papillary muscle)
Aneurysm (ventricle)
Pericarditis
Infaction (a second one)
Death/ Dressler's syndrome
Show Details / Rate It
---Dr. Huw Davies

Cardiovascular risk factors

FLASH BODIES:
Family history
Lipids
Age
Sex
Homocystinaemia
Blood pressure
Obesity
Diabetes mellitus
Inflammation (raised CRP)/ Increased thrombosis
Exercise
Smoking
Show Details / Rate It
---Hamish Mace Dunedin School of Medicine, New Zealand

Cardiovascular risk factors (Framingham)

FRAMINGHAM:
Family history
Running (exercise)
Adiposity (obesity)
Marlboros (tobacco)
Insulin resistance (diabetes)
Non-regulated lipids (dyslipidaemia)
Georgie Pie (high fat diet)
Hypertension
Age
Male

endocrine

Multiple Endocrine Neoplasia (MEN) subtype classification

Each subtype has 2 or 3 causes, plus something 1 or 2 more items.
MEN I is disease of 3 P's: [Pituitary, Parathyroid, Pancreas] plus one more: adrenal cortex.
MEN II is disease of 2 C's: [Carcinoma of thyroid, Catacholamines (pheochromocytoma)] plus two more: parathyroid for MEN IIa or mucocutaneous neuromas for MEN IIB (also called MEN III).
Show Details / Rate It
---Anonymous Contributor

Hypercalcemia: symptoms of elevated serum levels

"Bones, Stones, Groans, Moans":
Bones: pain in bones
Stones: renal
Groans: pain
Psychic moans/ Psychological overtones: confused state
Show Details / Rate It
---Anonymous Contributor

Pheochromocytoma: 3 most common symptoms

"PHEochromocytoma":
Palpitations
Headache
Edisodic sweating (diaphoresis)
Show Details / Rate It
---Anonymous Contributor

Thyroid carcinoma: features, prognosis of most popular

Most Popular is Papillary.
· Clinical features:
Papillae (branching)
Palpable lymph nodes
"Pupil" nuclei (Orphan Annie)
Psammoma bodies within lesion (often)
· Also, has a Positive Prognosis (10 year survival rate: 98%).
Show Details / Rate It
---Anonymous Contributor

Thyroid storm characteristics

"Storm HITS girls cAMP":
Thyroid storm due to:
Hyperthyroidism
Infection or Illness at childbirth
Trauma
Surgery
· girls: Thyroid storm more common in females.
· cAMP: Tx involves high dose of beta blockers (beta receptors work via cAMP)
· Alternatively: "S#IT storm": Surgery, Hyperthyroidism, Infection/ Illness, Trauma.
Show Details / Rate It
---Sung H. Kim & Lior Greenberg

Hypothyroidism/thyroiditis: maifestations and morphology

"A SCHISM among the Axis during WWII":
Addison disease
Subacute thyroiditis
Cretinism/ Cold intolerance/ Constipation
Hashimoto's disease
Infectious-subacute thyroiditis
Silent thyroiditis
Myxedema coma
· The Axis: Schimidt syndrome (when other endocrinology disorders accompany Hashimoto's disease) and "Hitler cells" (Hurthle cells, which are follicular epithelial cells with basophilic inculsions)
Show Details / Rate It
---Sung H. Kim

Cushing syndrome

CUSHING:
Central obesity/ Cervical fat pads/ Collagen fiber weakness/ Comedones (acne)
Urinary free corisol and glucose increase
Striae/ Suppressed immunity
Hypercortisolism/ Hypertension/ Hyperglycemia/ Hirsutism
Iatrogenic (Increased administration of corticosteroids)
Noniatrogenic (Neoplasms)
Glucose intolerance/ Growth retardation
Show Details / Rate It
---Rinku Uberoi

Calcification: metastatic vs. dystrophic

Metastatic: Metabolism imbalance.
Dystrophic: Damaged tissue.
Show Details / Rate It
---Anonymous Contributor

MEN I (Multiple Endocrine Neoplasia) syndrome: components

"Please Please Pay Attention To peptic ulceration, you worms":
· Adenomas of:
Pituatary
Pancreatic islets
Parathyroid
Adrenal cortex
Thyroid, associated with peptic ulceration
· Syndrome is called "Wermer's syndrome".
Show Details / Rate It
---Anonymous Contributor

Addison's disease: features

ADDISON:
Autoimmune
DIC (meningcoccus)
Destruction by cancer, infection, vascular insufficiency
Iatrogenic
Sarcoidosis, granulomatous such as TB histiomycosis
hypOtension/ hypOnatermia
Nelson's syndrome [post adrelectomy, increased ACTH]

Multiple endocrine neoplasia III: components

MEN III is a disease of 3 M's:
Medullary thyroid carcinoma
Medulla of adrenal (pheochromocytoma)
Mucosal neuroma
Show Details / Rate It
---Anonymous Contributor

Thyrotoxicosis syndrome: signs and symptoms

"A Penny For Every Symptom That Hyperthyroidism Will Make Grossly Evident":
Anxiety
Palpitations/ Pulse rapid
Fatigability
Emotional lability
Sweating
Tremor
Heat intolerance
Weight loss with good appetite
Muscular weakness/ Menstrual changes
Goitre
Eye changes
Show Details / Rate It
---Daniel Clarke University of Queensland

Goitre: differential

GOITRE:
Goitrogens
Onset of puberty
Iodine deficiency
Thyrotoxicosis/ Tumor/ Thyroiditis [Hashimoto's]
Reproduction [pregnancy]
Enzyme deficiencies
Show Details / Rate It
---Robert O'Connor University College Dublin

Adrenal disorders: Cushing's vs Addison's

Cushing: is Gushing cortisol.
In Addison's: patient's cortisol doesn't Add up.
Show Details / Rate It
---Anonymous Contributor

Pheochromocytoma: common symptoms

5 P's:
Paroxysmal rise in BP
Palpitations
Perspiration
Pain in abdomen
PMV in urine
Show Details / Rate It
---Malik Tariq Rahim King Edward Medical College, Pakistan

Phaeochromocytoma: diagnositc rule

· Rule of 10's:
10% ectopic
10% multiple
10% malignant
Show Details / Rate It
---Anonymous Contributor University of Sydney, Australia

Hirsutism vs. virilism

Hirsutism: Hair on body like a male.
Virilism: Voice and rest of secondary sexual characteristics like a male.
Show Details / Rate It
---Anonymous Contributor

Thyroid carcinoma: frequency

"Please Feel My A$$":
In order of most frequent to least frequent, and in order from least aggressive to most aggressive:
Papillary carcinoma
Follicular carcinoma
Medullary thyroid carcinoma
Anaplastic carcinoma
Show Details / Rate It
---Medicine 2004 student University of Western Ontario

Diabetes: short list of complications

SHAKE:
Stroke
Heart attack
Amputations
Kidney disease
Eyes (vision loss)

Lichen planus characteristics

Planus has 4 P's:
Peripheral
Polygonal
Pruritus
Purple
Show Details / Rate It
---Anonymous Contributor

Diabetic ketoacidosis: I vs. II

ketONE bodies are seen in type ONE diabetes.
Show Details / Rate It
---Anonymous Contributor

Baldness risk factors

"Daddy Doesn't Deny Getting Hair Implants":
Diet
Disease
Drugs
Genes
Hormones
Injury to the scalp
Show Details / Rate It
---Anonymous Contributor

Melanoma vs. basal cell, squamous cell carcinoma: metastatic ability

MElanoma is more likely to
MEtastasize.
· Basal and squamous hardly ever metastasize.
Show Details / Rate It
---Anonymous Contributor

Gout: factors that can precipitate an attack of acute gouty arthritis

DARK:
Diuretics
Alcohol
Renal disease
Kicked (trauma)
· And, the attack occurs most often at night [thus "dark"].
Show Details / Rate It
---Marc Miller Sackler School of Medicine

Renal failure: causes

AVID GUT:
Acute tubular necrosis
Vascular obstruction
Infection
Diffuse intravascular coagulation
Glomerular disease
Urinary obstruction
Tubulointerstitial nephritis
Show Details / Rate It
---Daniel Clarke University of Queensland

Calculi: types

CAlCUli:
Calcium
Ammonium magnesium phosphate
Cystine
Uric acid
Show Details / Rate It
---Robert O'Connor University College Dublin

Gout vs. pseudogout: crystal lab findings

Pseduogout crystals are:
Positive birefringent
Polygon shaped
· Gout therefore is the negative needle shaped crystals.
· Also, gout classically strikes great Toe, and its hallmark is Tophi.

Show Details / Rate It
---Robert O'Connor University College Dublin

APKD: signs, complications, accelerators

11 B's:
· Signs:
Bloody urine
Bilateral pain [vs. stones, which are usually unilateral pain]
Blood pressure up
Bigger kidneys
Bumps palpable
· Complications:
Berry aneurysm
Biliary cysts
Bicuspid valve [prolapse and other problems]
· Accelerators:
Boys
Blacks
Blood pressure high
Show Details / Rate It
---Robert O'Connor University College Dublin

Barter's syndrome: pathogenesis, major sign

Barter: "In exchange for giving away Na+,K+,Cl-, you can drop the blood pressure".
Show Details / Rate It
---Samuel Atom Baek-Kim Tuckahoe, New York

Renal failure (chronic): consequences

ABCDEFG:
Anemia
-due to less EPO
Bone alterations
-osteomalacia
-osteoporosis
-von Recklinghausen
Cardiopulmonary
-atherosclerosis
-CHF
-hypertension
-pericarditis
D vitamin loss
Electrolyte imbalance
-sodium loss/gain
-metabolic acidosis
-hyperkalemia
Feverous infections
-due to leukocyte abnormalities and dialysis hazards
GI disturbances
-haemorrhagic gastritis
-peptic ulcer disease
-intractable hiccups
Show Details / Rate It
---Plussind Siriraj Medical University, Thailand

Nephrotic syndrome: hallmark findings

"Protein LEAC":
Proteinuria
Lipid up
Edema
Albumin down
Cholesterol up
· In nephrotic, the proteins leak out.
Show Details / Rate It
---Anonymous Contributor

Gout: major features

GOUT:
Great toe
One joint (75% monoarticular)
Uric acid increased (hence urolithiasis)
Tophi
Show Details / Rate It
---Dr. Harsh Sharma BJ Medical College

Hematuria: urethral causes

NUTS:
Neoplasm
Urethritis
Tumour
Stone
Show Details / Rate It
---Sushant Varma University of Sheffield, UK

Gout: factors that can precipitate an attack of acute gouty arthritis

DARK:
Diuretics
Alcohol
Renal disease
Kicked (trauma)
· And, the attack occurs most often at night [thus "dark"].
Show Details / Rate It
---Marc Miller Sackler School of Medicine

Renal failure: causes

Calculi: types

CAlCUli:
Calcium
Ammonium magnesium phosphate
Cystine
Uric acid
Show Details / Rate It
---Robert O'Connor University College Dublin

Gout vs. pseudogout: crystal lab findings

APKD: signs, complications, accelerators

Barter's syndrome: pathogenesis, major sign

Barter: "In exchange for giving away Na+,K+,Cl-, you can drop the blood pressure".
Show Details / Rate It
---Samuel Atom Baek-Kim Tuckahoe, New York

Renal failure (chronic): consequences

Nephrotic syndrome: hallmark findings

"Protein LEAC":
Proteinuria
Lipid up
Edema
Albumin down
Cholesterol up
· In nephrotic, the proteins leak out.
Show Details / Rate It
---Anonymous Contributor

Gout: major features

GOUT:
Great toe
One joint (75% monoarticular)
Uric acid increased (hence urolithiasis)
Tophi
Show Details / Rate It
---Dr. Harsh Sharma BJ Medical College

Hematuria: urethral causes

NUTS:
Neoplasm
Urethritis
Tumour
Stone
Show Details / Rate It
---Sushant Varma University of Sheffield, UK

Hodgkin's lymphoma classification

A: Asymptomatic
B: Bad
Show Details / Rate It
---Anonymous Contributor

Wiskott-Aldrich syndrome: symptom triad

"PET WASP":
Pyrogenic infections
Eczema
Thrombocytopenia
· WASP is the name of the causitive agent: Wiskott-Aldrich Syndrome Protein.
· Alternatively: Wiskott=Hot, Aldrich=Itch, Syndrom=Throm.
Show Details / Rate It
---Robert O'Connor University College Dublin

Sarcoidosis summarized

SARCOIDOISIS:
Schaumann calcifications
Asteroid bodies/ [ACE] increase/ Anergy
Respiratory complications/ Renal calculi/ Restrictive lung disease/ Restrictive cardiomyopathy
Calcium increase in serum and urine/ CD4 helper cells
Ocular lesions
Immune mediated noncaseating granulomas/ [Ig] increase
Diabetes insipidus/ [D vit.] increase/ Dyspnea
Osteopathy
Skin (Subcutaneous nodules, erythema nodosum)
Interstitial lung fibrosis/ IL-1
Seventh CN palsy
Show Details / Rate It
---Rinku Uberoi UNIBE

Apoptosis vs. necrosis

"LIFELESS" (since cells are dead):
· Differences are in:
Leaky membranes
Inflammatory response
Fate
Extent
Laddering
Energy dependent
Swell or shrink
Stimulus
· See attached table for apoptosis and necrosis properties for each of the above.

Show Details / Rate It
---Robert O'Connor University College Dublin

Leukemias: acute vs. chronic rules of thumb

ABCDE:
Acute is:
Blasts predominate
Children
Drastic course
Elderly
Few WBC's (so Fevers)
· Chronic is all the opposites:
Mature cells predominate
Middle aged
Less debilitating course
Elevated WBC's, so not a history of fevers and infections
Show Details / Rate It
---Anonymous Contributor

Hypersplenism: criteria

"Hyper Splenism Ravages Cells":
Hypercellular or normal marrow
Splenomegaly
Response to splenectomy
Cytopenias
Show Details / Rate It
---Dr. Harsh Sharma BJMC, Pune, India

Anemia: TIBC finding to differentiate iron deficiency vs. chronic disease

TIBC levels at the:
Top=Iron deficiency.
Bottom=Chronic disease.
Show Details / Rate It
---Robert O'Connor University College Dublin

Microcytic anemia: causes

"Find Those Small Cells":
Fe deficiency
Thalassemia
Sideroblastic
Chronic disease
Show Details / Rate It
---K. Dang University of Toronto

Megaloblastic anemia: vitamin B12 deficiency vs. folate deficiency

Vitamin B12 deficiency also affects Brain (optic neuropathy, subacute combined degeneration, paresthesia).
· Folate deficiency is not associated with neurological symptoms.
Show Details / Rate It
---Glen Davis Cornell University Medical College

Symptoms of TTP/HUS

"Nasty Fever Ruined My Tubes":
Neurological symptoms
Fever
Renal failure
Microangiopathic hemolytic anemia
Thrombocytopenia

Hemophilia: type A factor

Hemophilia A: problems with VIII factor (number V as an inverted A).
Show Details / Rate It
---Julio M. De Peña, M.D. UNIBE Med School

Wiskott-Aldrich syndrome: symptom triad

WASTER:
Wiskott Aldrich Syndrome is:
Thrombocytopenia
Eczema
Recurrent staphlococcal infections
Show Details / Rate It
---Anonymous Contributor

Macrocytosis: Non-B12/folate causes

ALPHA NERD:
Alcohol
Liver disease
Pregnancy
Hemaolysis (especially chronic)
Agglutination
Neoplasia (including myelodysplasia)
Endocrine (hypothyroidism)
Reticulocytes
Drugs (especially myelosuppressives like chemotherapy, anti-HIV meds)
Show Details / Rate It
---Steve

Duchenne vs. Becker Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) : Doesn't Make Dystrophin.
Becker Muscular Dystrophy (BMD): Badly Made Dystrophin (a truncated protein).
Show Details / Rate It
---Robert O'Connor University College Dublin

McArdle's syndrome

MCARDLES:
Myoglobinuria
Cramping after exercise
Accumulated glycogen
Recessive inheritance
Deficiency of muscle phosphorylase
Lactate levels fail to rise
Elevated creatine kinase
Skeletal muscle only

Nervous system

Wernicke-Korsakoff triad

Syndrome in alchoholics, who love to "drink CANs of beer":
Confusion
Ataxia
Nystagmus
Show Details / Rate It
---Victor R. Carrion Zamoira Ponce School of Medicine

Wernicke-Korsakoff's psychosis: findings

COAT RACK:
· Wernicke's encephalopathy (acute phase):
Confusion
Ophthalmoplegia
Ataxia
Thiamine tx.
· Korsakoff's psychosis (chronic phase):
Retrograde amnesia
Anterograde amnesia
Confabulation
Korsakoff's psychosis
Show Details / Rate It
---HBV Morehouse School of Medicine

Parkinsonism: essential features

TRAPS:
Tremor (resting tremor)
Rigidity
Akinesia
Postural changes (stooped)
Stare (serpentine stare)
· To remember what kind of tremor and postural change, can look at letter that follows in TRAPS: Tremor is Resting, Posture is Stooped.
Show Details / Rate It
---Anonymous Contributor

Tabes Dorsalis morphology

DORSALIS:
Dorsal column degeneration
Orthopedic pain (Charcot joints)
Reflexes decreased (deep tendon)
Shooting pain
Argyll-Robertson pupils
Locomotor ataxia
Impaired proprioception
Syphilis
Show Details / Rate It
---Robert O'Connor University College Dublin

Pyrogenic meningitis: likeliest bug in age group

"Explaining Hot Neck Stiffness":
· In order from birth to death:
E. coli [infants]
Haemophilus influenzae [older infants, kids]
Neisseria meningitis [young adults]
Streptococcus pneumoniae [old folks]
Show Details / Rate It
---Robert O'Connor University College Dublin

Parkinson's disease: symptoms

PQRST:
Paucity of expression
parQinson
Rigidity (cogwheel)
Stooped posture
Tremor at rest
· If can't remember that Parkinson's tremor is the one that is "resting tremor", look at the last 3 letters: RST.
Show Details / Rate It
---Mitul SUNY, Stony Brook

Neuroblastoma: features

N-MYC:
Nuclei have "double minutes"
Malignant
Young
Catecholamine secreting
· And hallmark is n-myc amplification.
Show Details / Rate It
---Robert O'Connor University College Dublin

Lou Gehrig's is both upper and lower motor neuron signs

LoU = Lower & Upper.
Show Details / Rate It
---Robert O'Connor University College Dublin

Dandy-Walker syndrome: components

"Dandy Walker Syndrome":
Dilated 4th ventricle
Water on the brain
Small vermis
Show Details / Rate It
---Robert O'Connor University College Dublin

Cerebral palsy: general features

PALSY:
Paresis
Ataxia
Lagging motor development
Spasticity
Young
Show Details / Rate It

Multiple sclerosis (MS): pathology

MS attacks the Myelin Sheath, resulting in plaques.
Show Details / Rate It
---Lior Greenberg Technion Faculty of Medicine, Haifa, Israel

Alzheimer's disease: features

RONALD (Ronald Reagan, a famous victim):
Reduction of Ach
Old age
Neurofibrillary tangles
Atrophy of cerebral cortex (diffuse)
Language impairment
Dementia (MC in elderly)/ Down's syndrome
Show Details / Rate It
---Dr. Harsh Sharma BJMC, Pune, India

Pick's disease: features

PICK:
Progressive degeneration of neurons
Intracytoplasmic Pick bodies
Cortical atrophy
Knife edge gyri
Show Details / Rate It
---Dr. Atif Farooq Khawaja Rawalpindi Medical College, Pakistan

Alzheimer's disease (AD): associations, findings

AD:
· Associations:
Aluminum toxicity
Acetylcholine deficiencies
Amyloid B
Apolipoprotein gene E
Altered nucleus basalis of Meynert
Down's
· Findings:
Actin inclusions (Hirano bodies)
Atrophy of brain
Amyloid plaques
Aphasia, Apraxia, Agitation
DNA-coiled tangles
Dementia, Disoriented, Depressed
Show Details / Rate It
---Dr. Atif Farooq Khawaja Rawalpindi Medical College, Gujranwala, Pakistan

Wernickes encephalopathy: components

WACO:
· Wernickes is:
Ataxia
Confusion (or clouded consciousness)
Ocular problems
· Note: Waco is the town in Texas, USA made famous for a standoff with a David Koresh and the Branch Davidians.
Show Details / Rate It

Other

Necrosis: the 4 types

"Life Can Get Complicated":
Liquifactive
Coagulation
Gangrene
Caseous
· 'Life' used since necrosis is 'death'.
Show Details / Rate It
---Robert O'Connor University College Dublin

Turner syndrome: components

CLOWNS:
Cardiac abnormalities (specifically Coartication)
Lymphoedema
Ovaries underdeveloped (causing sterility, amenorrhea)
Webbed neck
Nipples widely spaced
Short

Show Details / Rate It
---Robert O'Connor University College Dublin

Fragile-X syndrome: features

DSM-4:
Discontinued chromosome staining
Shows anticipation
Male (male more affected)
Mental retardation (2nd most common genetic cause)
Macrognathia
Macroorchidism
Show Details / Rate It
---Hugo M. Rodriguez, MD University of Virginia Roanoke-Salem Program

Whipple's disease: full features

WHIPPLES:
Weight loss
Hyperpigmentation of skin
Infection with tropheryma whippelii
PAS positive granules in macrophage
Polyarthritis
Lymphadenopathy
Enteric involvement
Steatorrhea
Show Details / Rate It
---Dr. Atif Farooq Khawaja Rawalpindi Medical College, Pakistan

CREST sydrome: components

CREST:
Calcinosis
Raynaud's phenomena
Esophageal dysmotility
Sclerodactyly
Telangectasia
Show Details / Rate It
---Andrew J. Vasil University of Minn Medical School

Edwards' syndrome: characteristics

EDWARDS:
Eighteen (trisomy)
Digit overlapping flexion
Wide head
Absent intellect (mentally retarded)
Rocker-bottom feet
Diseased heart
Small lower jaw
Show Details / Rate It
---Monika Kiripolsky Vanderbilt University School of Medicine

Fragile X syndrome: features

FEMALES
FMR1 gene
Exhibits anticpation
Macro-orchidism
Autism
Long face with large jaw
Everted eyes
Second most common casue of genetic mental retardation
Show Details / Rate It
---Sung Hoon Kim El Paso, TX

Kawasaki Disease Criteria

"Be careful when riding a Kawasaki motorcycle, you might get CREAMed.
Conjunctivitis (non-exudative)
Rash (polymorphous non-vesicular)
Edema (or erythema of hands or feet)
Adenopathy (cervical, often unilateral)
Mucosal involvement (erythema or fissures or crusting)
To have Kawasaki disease you must have fever for greater than 5 days plus 4 of the above.
Show Details / Rate It
---Eric J Ex

Neurofibromatoses: chromosome mutation locations in von Reckinghausen (type I) vs. type II

"von Recklinghausen" has 17 letters and is due to a mutation on chromosome 17.
"Neurofibromatosis type 2" has 22 and is due to a mutation on chromosome 22.
Show Details / Rate It
---Anonymous Contributor UAG

Pulmonary

Pulmonary embolism: risk factors

TOM SCHREPFER:
Trauma
Obesity
Malignancy
Surgery
Cardiac disease
Hospitalization
Rest [bed-ridden]
Elderly
Past history
Fracture
Estrogen [pregnancy, post-partum]
Road trip
Show Details / Rate It
---Anonymous Contributor

Respiratory distress syndrome in infants: major risk factors

PCD (Primary Ciliary Dyskinesia, a cause of Respiratory distress syndrome):
Prematurity
Cesarean section
Diabetic mother
Show Details / Rate It
---Shebrain Cairo University

Emphysema: types, most important feature of each

"Cigarettes Is Primary Problem":
· Types:
Centrilobular
Irregular
Pancinar
Paraseptal
· Most important feature for each type (in order as above):
Cigarrettes
Inflammation healed to scar
Protease inhibitor deficiency (a1-antitrypsin)
Pneumothorax
· "Cigarettes is primary problem" used since cigarettes is most common cause of emphysema.
· Keeping P's straight: Pan is antitrypsin.
Show Details / Rate It
---Robert O'Connor University College Dublin

COPD: 4 types and hallmark

ABCDE:
Asthma
Brochiectasis
Chronic bronchitis
Dyspnea [hallmark of group]
Emphysema
· Alternatively: replace Dyspnea with Decreased FEV1/FVC ratio.
Show Details / Rate It
---Robert O'Connor University College Dublin

Lung cancer: presentation

ABCDE:
Snowball turned to Avalanche
Blood: hemoptysis
Cough
Distruption to airway in bronchus-->pneumonia
whEEzing
Show Details / Rate It
---Samuel Atom Baek-Kim

Interstitial lung disease: causes

SARCOIDI:
Sarcoidosis
Allergic reaction
Radiation
Connective tissue disease
Occupational exposure
Infection
Drugs
Idiopathic

Show Details / Rate It
---Will Herrington UCL Hospital

Bronchial obstruction: consequences

APPLE BABE:
Atelectasis
Pleural adhesions
Pleuritis
Lipid pneumonia
Effusion->organisation->fibrosis
Bronchiectasis
Abscess
Broncho and lobar pneumonia
Emphysema
Show Details / Rate It
---BB University of Queensland, Australia

Nasopharyngeal malignant cancers

NASOPharyngeal:
Nasophayngeal
Adenocarcinoma
Squamous cell carcinoma
Olfactory neuroblastoma
Plasmacytoma
Show Details / Rate It
---Robert O'Connor University College Dublin

TB: features

TB is characterised by 4 C's:
Caseation
Calcification
Cavitation
Cicatrization
Show Details / Rate It
---Sameh Shehata Asst. Prof of Surgery, Faculty of Medicine, University of Alexandria, Egypt

Pancoast tumor: relationship with Horner's syndrome

"Horner has a MAP of the Coast":
A panCoast tumor is a cancer of the lung apex that compresses the cervical sympathetic plexus, causing Horner's syndrome, which is MAP:
Miosis
Anhidrosis
Ptosis

Pulmonary fibrosis: differential of both upper and lower lobes

BREAST SCAR:
· Upper lobe:
Beryliosis
Radiation
Extrinsic allergic alveolitis
Ankylosing spondylitis
Sarcoidosis
TB
· Lower lobe:
Systemic sclerosis
Cryptogenic fibrosing alveolitis
Asbestosis
Radiation
Show Details / Rate It
---Lyndon Mason 4th Year Medical Student

Pulmonary embolism: risk factors

7 H's:
Hereditary (eg factor V Leyden, protein C or S deficiency)
History (previous DVT or PE)
Hypomobility (fracture, CVA, severe illness, obesity, long trip)
Hypovolaemia (nephrotic syndrome, dehydration)
Hypercoagulability (smoking, malignancy)
Hormones (oestrogens [esp. in OCP], puerperium)
Hyperhomocysteinaemia
Show Details / Rate It
---Fahed Al-Daour Med Student

Pneumothorax: presentation

P-THORAX:
Pleuretic pain
Trachea deviation
Hyperresonance
Onset sudden
Reduced breath sounds (& dypsnea)
Absent fremitus
X-ray shows collapse
Show Details / Rate It
---Robert O'Connor University College Dublin

COPD: blue bloater vs. pink puffer diseases

emPhysema has letter P (and not B) so Pink Puffer.
chronic Bronchitis has letter B (and not P) so Blue Bloater.
Show Details / Rate It
---Harsh Sharma BJMC, Pune, India

Adult Respiratory Distress Syndrome (ARDS): causes

ARDS:
Aspiration/ Acute pancreatitis/ Air embolism/ Amniotic embolism
Radiation
DIC/ Drugs/ Drowning/ Dialysis/ Diffuse lung infection
Shock/ Sepsis/ Smoke inhalation
Show Details / Rate It

reproductive

Breast cancer: risk assessment

"Risk can be assessed by History ALONE":
History (family, previous episode)
Abortion/ Age (old)
Late menopause
Obesity
Nulliparity
Early menarche
Show Details / Rate It
---Lau Yue Young Geoffrey Hong Kong University

Endometrial carcinoma: risk factors

ENDOMET:
Elderly
Nulliparity
Diabetes
Obesity
Menstrual irregularity
Estrogen therapy
hyperTension
Show Details / Rate It
---Robert O'Connor University College Dublin

Polycystic ovary: morphology, presentation

· Morphology is poly-C:
Cysts
Capsule thickened
Cortical stromal fibrosis
· Clinical presentation is OVARY:
Obese
Virilism or hirsutism
Amenorrhoea
Reproductive problem [infertile]
Young woman
Show Details / Rate It
---Robert O'Connor University College Dublin

Herpes I and II: lab findings.

She's an odd chick: whenever she's in a restaurant, she always orders Her Peas and Cow dry.
Herpes I and II have Cowdry Type A inclusion bodies
Show Details / Rate It
---Lior Greenberg Technion Faculty of Medicine, Haifa, Israel

Gynecomastia: causes

DaLAS:
Digitalis
Leydig cell tumors
Alcohol
Sertoli cell tumors
Show Details / Rate It
---Chris Jordan UAG

Scrotum masses

SHOVE IT:
Spermatocele
Hydrocele/ Haematocele
Orchitis
Varicocele
Epidymal cyst
Indirect inguinal hernia
Torsion/ Tumor
Show Details / Rate It
---Sushant Varma Medical student, University of Sheffield, UK

Ovarian cancers: important types, by WHO classification

· Surface:
"My Sister Began Experiencing Cancer":
Mucinous
Serous
Brenner
Endometrioid
Clear
· Germ cell:
"Doctor Examined The Ovaries":
Dysgerminoma
Endometrial sinus
Teratoma
Ovarian choriocarcinoma
· Sex cord:
"She Felt Grim":
Sertoli-Leydig
Fibroma
Granulosa-theca
· Metastatic
"Killed":
Krukenberg
Show Details / Rate It
---Edward Scarth Medical School, Univeristy of Nottingham

Endometrial carcinoma: risk factors

HONDA:
Hypertension
Obesity
Nulliparity
Diabetes
Age (increased)
Show Details / Rate It
---Sarah

Polycystic ovarian disease: clinical features

OHIO:
Oligomenorrhea
Hirsutism
Infertility
Obesity

Skeletal

Paget's disease of bone: signs and symptoms

Four L's:
Larger hat size
Loss of hearing: due to compression of nerve
Leontiasis ossea (lion-like face)
Light-headed (Paget's steal)
Show Details / Rate It
---Marc Miller Sackler School of Medicine

Carcinomas having tendency to metastasize to bone

"Particular Tumours Love Killing Bone":
Prostate
Thyroid
Lung
Kidney
Breast
Show Details / Rate It
---Ben Campbell University of Otago Medical School, Dunedin, New Zealand

Rheumatoid arthritis: features

RHEUMATOID:
Ragocytes/ Rheumatoid factor (anti-IgG)
HLA-DR4/ HLA-Dw4
ESR increase/ Extra-articular features (restrictive lung disease, subcutaneous nodules)
Ulnar deviation
Morning stiffness/ MCP joint
Ankylosis/ Atlantoaxial joint subluxation/ Autoimmune/ ANA
T-cells (CD4)/ TNF
Osteopenia
Inflammatory synovial tissue/ Idiopathic/ IL-1
Deformities (swan-neck, boutonniere)
Show Details / Rate It
---Rinku S. Uberoi UNIBE

Marble bone disease: signs and symptoms

MARBLES:
Multiple fractures
Anemia
Restricted cranial nerves
Blind & deaf
Liver enlarged
Erlenmeyer flask deformity
Splenomegaly
· Eponymous name: Marbles = Albers-Schonberg (anagram).
Show Details / Rate It
---Robert O'Connor University College Dublin

Histiocytosis X: hallmark finding

"Birbeck's rackets is X":
Tennis rackets under electron microscope is Histiocystosis X.
Consider 2 tennis rackets in an X formation.
· See diagram.

Show Details / Rate It
---Robert O'Connor University College Dublin

Seronegative spondyloarthopathy: diseases

RAPE:
Reiter's syndrome
Ankylosing spondylitis
Psoriatic arthitis
Enteropathic arthitis (IBD)
Show Details / Rate It
---Wen Sun Lum University of Calgary, Canada

Osteomalacia: features

"Vit-D deficiency in ADULT":
Acetabuli protrusio
Decresed bone density
Under mineralization of osteoid
Looser's zone (pseudofracture)
Triradiate pelvis (females)
Show Details / Rate It
---Dr. Harsh Sharma BJMC, Pune, India

Osteosarcoma: features

PEARL HARBOR:
Paget's disease (10-20%)*
Early age (10-20 yrs)
Around knee
Raised periosteum by expanding tumor: "sunburst pattern"
Lace-like architecture
Hyaline arteoriosclerosis
Alkaline phosphatase increased
Retinoblastoma*
Boys, predominantly
Osteomyelitis DDx
Radiation*
· Sunburst pattern was Japanese Navy emblem during WWII.
*: Predisposing factors.
Show Details / Rate It
---Sung H. Kim El Paso, TX

Osteomyelitis: complications

FIBRES:
Fractures
Intraosseous (broidie) abscesses
Bacteremi/ Brodie abscess
Reactive amyloidosis
Endocarditis
Sinus tracts/ Squamous cell CA

resealed erythrocytes

2010-11-13T11:14:00.000-08:00

RESEALED ERYTHROCYTES

INTRODUCTION

Erythrocytes, also known as red blood cells, have been extensively studied for their potential carrier capabilities for the delivery of drugs and drug-loaded microspheres Such drug-loaded carrier erythrocytes are prepared simply by collecting blood samples from the organism of interest, separating erythrocytes from plasma, entrapping drug in the erythrocytes, and resealing the resultant cellular carriers. Hence, these carriers are called resealed erythrocytes. The overall process is based on the response of these cells under osmotic conditions. Upon reinjection, the drug-loaded erythrocytes serve as slow circulating depots and target the drugs to a reticuloendothelial system (RES)

Morphology and physiology of erythrocytes

Erythrocytes are the most abundant cells in the human body (5.4 million cells/mm3 bloods in a healthy male and _4.8 million cells/mm3 bloods in a healthy female). These cells were described in human blood samples by Dutch Scientist Lee Van Hock in 1674. In the 19th century, Hope Seyler identified hemoglobin and its crucial role in oxygen delivery to various parts of the body. Erythrocytes are biconcave discs with an average diameter of 7.8 _m, a thickness of 2.5 _m in periphery, 1 _m in the center, and a volume of 85–91 _m3 (7). The flexible, biconcave shape enables erythrocytes to squeeze through narrow capillaries, which may be only 3 _m wide. Mature erythrocytes are quite simple in structure. They lack a nucleus and other organelles. Their plasma membrane encloses hemoglobin, a heme-containing protein that is responsible for O2–CO2 binding inside the erythrocytes. The main role of erythrocytes is the transport of O2 from the lungs to tissues and the CO2 produced in tissues back to lungs. Thus, erythrocytes are a highly specialized O2 carrier system in the body. Because a nucleus is absent, all the intracellular space is available for O2 transport. Also, because mitochondria are absent and because energy is generated anaerobically in erythrocytes, these cells do not consume any of the oxygen they are carrying. Erythrocytes live only about 120 days because of wear and tear on their plasma membranes as they squeeze through the narrow blood capillaries. Worn-out erythrocytes are removed from circulation and destroyed in the spleen and liver (RES), and the breakdown products are recycled. The process of erythrocyte forma-tion within the body is known as erythropoiesis. In a mature human being, erythrocytes are produced in red bone marrow under the regulation of a hemopoietic hormone called erythropoietin (8).

Source and isolation of erythrocytes

Various types of mammalian erythrocytes have been used fordrug delivery, including erythrocytes of mice, cattle, pigs, dogs, sheep, goats, monkeys, chicken, rats, and rabbits. To isolate erythrocytes,blood is collected in heparinized tubes by venipuncture.Fresh whole blood is typically used for loading purposes because the encapsulation efficiency of the erythrocytes isolated from fresh blood is higher than that of the aged blood. Fresh whole blood is the blood that is collected and immediately chilled to 4 _C and stored for less than two days. The erythrocytes are then harvested and washed by centrifugation. The washed cells are suspended in buffer solutions at various hematocrit values as desired and are often stored in acid–citrate–dextrose buffer at 4C for as long as 48 h before use. Jain and Vyas have described a well-established protocol for the isolation of erythrocytes In 1953, Gardos tried to load erythrocyte ghost using adenosine triphosphate (ATP). In 1959, Marsden and Ostting reported the entrapment of dextran (molecular weight 10–250kDa). In 1973, the loading of drugs in erythrocytes was reportedseparately by Ihler et al. and Zimmermann. In 1979, the term carrier erythrocytes were coined to describe drug-loaded erythrocytes.

Advantages of erythrocytes as drug carriers

Advantages include:

their biocompatibility, particularly when autologous cells are used, hence no possibility of triggered immune response
their biodegradability with no generation of toxic products
the considerably uniform size and shape of the carrier
relatively inert intracellular environment
prevention of degradation of the loaded drug from inactivation by endogenous chemicals
the wide variety of chemicals that can be entrapped,
the modification of pharmacokinetic and pharmacodynamic parameters of drug
attainment of steady-state plasma concentration decreases fluctuations in concentration
Protection of the organism against toxic effects of drugs (e.g.antineoplastics,).

Other advantages are:

Ø their ability to circulate throughout the body

Ø the availability of the techniques and facilities for separation, handling, transfusion, and working with erythrocytes

Ø the prevention of any undesired immune response against the loaded drug

Ø their ability to target the organs of the RES

Ø the possibility of ideal zero-order drug-release kinetics

Ø the lack of occurrence of undesired immune response against encapsulated drug

Ø the large quantity of drug that can be encapsulated within a small volume of cells ensures dose sufficiency

Ø a longer life span in circulation as compared with other synthetic carriers and optimum conditions may result in the life span comparable to that of normal erythrocytes

Ø easy control during life span ranging from minutes to months

Ø a decrease in side effects of drugs

Ø a considerable increase in drug dosing interval with drug residing in therapeutic window region for longer time periods

Methods of drug loading Several methods can be used to load drugs or other bioactive compounds in erythrocytes, including physical (e.g., electrical pulse method) osmosis-based systems, and chemical methods (e.g., chemical perturbation of the erythrocytes membrane). Irrespective of the method used, the optimal characteristics for the successful entrapment of the compound requires the drug to have a considerable degree of water solubility, resistance against degradation within erythrocytes, lack of physical or chemical interaction with erythrocyte membrane, and well-defined pharmacokinetic and pharmacodynamic properties

Hypotonic hemolysis. This method is based on the ability of erythrocytes to undergo reversible swelling in a hypotonic solution. Erythrocytes have an exceptional capability for reversible shape changes with or without accompanying volume change and for reversible deformation under stress. An increase in volume leads to an initial change in the shape from biconcave to spherical. This change is attributable to the absence of superfluous membrane, hence, the surface area of the cell is fixed. The cells assume a spherical shape to accommodate additional volume while keeping the surface area constant. The volume gain is _25–50%. The cells can maintain their integrity up to a tonicity of _150 mosm/kg, above which the membrane ruptures, releasing the cellular contents. At this point (just before cell lysis), some transient pores of 200–500 Å are generated on the membrane. After cell lysis, cellular contents are depleted. The remnant is called an erythrocyte ghost the principle of using these ruptured erythrocytes as drug carriers is based on the fact that the ruptured membranes can be resealed by restoring isotonic conditions. Upon incubation, the cells resume their original biconcave shape and recover original impermeability

Use of red cell loader. Magnani et al. developed a novel method for entrapment of nondiffusible drugs into erythrocytes. They developed a piece of equipment called a “red cell loader”. With as little as 50 mL of a blood sample, different biologically active compounds were entrapped into erythrocytes within a period of 2 h at room temperature under blood banking conditions. The process is based on two sequential hypotonic dilutions of washed erythrocytes followed by concentration with a hemofilter and an isotonic resealing of the cells. There was _30% drug loading with 35–50% cell recovery. The processed erythrocytes had normal survival in vivo. The same cells could be used for targeting by improving their recognition by tissue macrophages.

Hypotonic dilution. Hypotonic dilution was the first method investigated for the encapsulation of chemicals into erythrocytes and is the simplest and fastest In this method, a volume of packed erythrocytes is diluted with 2–20 volumes of aqueous solution of a drug. The solution tonicity is then restored by adding a hypertonic buffer. The resultant mixture is then centrifuged, the supernatant is discarded, and the pellet is washed with isotonic buffer solution). The major drawbacks of this method include a low entrapment efficiency and a considerable loss of hemoglobin and other cell components this reduces the circulation half life of the loaded cells. These cells are readily phagocytosed by RES macrophages and hence can be used for targeting RES organs hypotonic dilution is used for loading enzymes such as _-galactosidase and glucosidase asparginase and arginase. As well as bronchodilators such as salbutamol

Hypotonic preswelling. This method was developed by Rechsteiner in 1975 and was modified by Jenner et al. for drug loading. The technique is based upon initial controlled swelling in a hypotonic buffered solution. This mixture is centrifuged at low g values. The supernatant is discarded and the cell fraction is brought to the lysis point by adding 100–120 _L portions of an aqueous solution of the drug to be encapsulated. The mixture is centrifuged between the drug-addition steps. The lysis point is detected by the disappearance of a distinct boundary between the cell fraction and the supernatant upon centrifugation. The tonicity of a cell mixture is restored at the lysis point by adding a calculated amount of hypertonic buffer. Then, the cell suspension is incubated at 37 _C to reanneal the resealed erythrocytes. Such cells have a circulation half life comparable to that of normal cells this method is simpler and faster than other methods, causing minimum damage to cells. Drugs encapsulated in erythrocytes using

This method includes propranolol, asparginase, cyclopohphamide, cortisol-21-phosphate, _1 antitrypsin methotrexate, insulin in 1959 and was used in 1977 by Deloach and Ihler, and Dale for loading enzymes and lipids. Severalmethods are based on the principle that semipermeable dialysis membrane maximizes the intracellular: extracellular volume ratio for macromolecules during lysis and resealing. In the process, an isotonic, buffered suspension of erythrocytes with

a hematocrit value of 70–80 is prepared and placed in a conventional dialysis tube immersed in 10–20 volumes of a hypotonic buffer. The medium is agitated slowly for 2 h. The tonicity of the dialysis tube is restored by directly adding a calculated amount of a hypertonic buffer to the surrounding medium or by replacing the surrounding medium by isotonic buffer. The drug to be loaded can be added by either dissolving the drug in isotonic cell suspending buffer inside a dialysis bag at the beginning of the experiment or by adding the drug to a dialysis bag after the stirring is complete. The use of standard hemodialysis equipment for loading a drug in erythrocytes was reported by Roper et al. In this method, the erythrocyte suspension and the drug to be loaded were placed in the blood compartment and the hypotonic buffer was placed in a receptor compartment. This led to the concept of “continuous flow dialysis,” which has been used by several other researchers. The loaded cells exhibit the same circulation half life as that of normal cells. Also, this method has high entrapment efficiency on the order of 30–50% cell recovery of 70–80%, high-loading capacity, and is amenable to automation with control of process variables. The drawbacks include a long processing time and the need for special equipment .This method has been used for loading enzymes such as _- galactosidase, glucoserebrosidase , asparginase, inositol hexaphosphatase , as well as drugs such as gentamicin , adriamycin , interlukin-2, desferroxamine , and human

Isotonic osmotic lysis.This method, also known as the osmotic pulse method, involves isotonic hemolysis that is achieved by physical or chemical means. The isotonic solutions may or may

Not be isoionic. If erythrocytes are incubated in solutions of a substance with high membrane permeability, the solute will diffuse into the cells because of the concentration gradient. This

Process is followed by an influx of water to maintain osmotic equilibrium. Chemicals such as urea solution, polyethylene glycol, and ammonium chloride have been used for isotonic hemolysis. However, this method also is not immune to changes in membrane structure composition. In 1987, Franco et al. developed a method that involved suspending erythrocytes in an isotonic solution of dimethyl sulfoxide (DMSO). Thesuspension was diluted with an isotonic-buffered drug solution. After the cells were separated, they were resealed at 37 _C.

Chemical perturbation of the membrane. This method is based on the increase in membrane permeability of erythrocytes when the cells are exposed to certain chemicals. In 1973, Deuticke et al. showed that the permeability of erythrocytic membrane increases upon exposure to polyene antibiotic such as amphotericin B. In 1980, this method was used successfully by Kitao and Hattori to entrap the antineoplastic drug daunomycin in human and mouse erythrocytes. Lin et al used halothane for the same purpose. However, these methods induce irreversible destructive changes in the cell membrane and hence are not very popular.

Electro-insertion or electroencapsulation. In 1973, Zimmermann tried an electrical pulse method to encapsulate bioactive molecules. Also known as electroporation, the method is based on the observation that electrical shock brings about irreversible changes in an erythrocyte membrane. In 1977, Tsong and Kinosita suggested the use of transient electrolysis to generate desirable membrane permeability for drug loading. The erythrocyte membrane is opened by a dielectric breakdown. Subsequently, the pores can be resealed by incubation at 37 _C in an isotonic medium. The procedure involves suspending erythrocytes in an isotonic buffer in an electrical discharge chamber. A capacitor in an external circuit is charged to a definite voltage and then dischargedwithin a definite time interval through cell suspension to produce a square-wave potential. The optimum intensity of an electric field is between 1–10 kW/cm and optimal discharge time is between 20–160 _s. An inverse relationship exists between the electric-field intensity and the discharge time. The compound to be entrapped is added to the medium in which the cells are suspended from the commencement of the experiment. The characteristic pore diameter created in the membrane depends upon the intensity of electric field, the discharge time, and the ionic strength of suspending medium. The colloidal macromolecules contents of the cell may lead to cell lysis because of the increase in osmotic pressure. This process can be prevented by adding large molecules (e.g., tetrasaccharide stachyose and bovine serum albumin) and ribonucleose. One advantage of this method is a more uniform distribution of loaded cells in comparison with osmotic methods. The main drawbacks are the need for special instrumentation and the sophistication of the process. Entrapment efficiency of this method is _35%, and the life span of the resealed cells in circulation is comparablewith that of normal cells.Various compounds such as sucrose, urease, methotrexate, isoniazid, human glycophorin, DNA fragments, and latex particles of diameter 0.2 _m can be entrapped within erythrocytes by this method. Mangal and Kaur achieved sustained release of a drug entrapped in erythrocytes with

the use of electroporation.

Entrapment by endocytosis. This method was reported by Schrier et al. in 1975. Endocytosis involves the addition of one volume of washed packed erythrocytes to nine volumes of buffer containing 2.5 mM ATP, 2.5 mM MgCl2, and 1mM CaCl2, followed by incubation for 2 min at room temperature. The pores created by this method are resealed by using 154 mM of NaCl and incubation at 37 _C for 2 min. The entrapment of material occurs by endocytosis. The vesicle membrane separates endocytosed material from cytoplasm thus protecting it from the erythrocytes and vice-versa. The various candidates entrapped by this method include primaquine and related 8–amino–quinolines, vinblastine, chlorpromazine and related phenothiazines, hydrocortisone, propranolol, tetracaine,and vitamin A.

Loading by electric cell fusion. This method involves the initial loading of drug molecules into erythrocyte ghosts followed by adhesion of these cells to target cells. The fusion is accentuated by the application of an electric pulse, which causes the release of an entrapped molecule.An example of this method is loading a cell-specific monoclonal antibody into an erythrocyte ghost). An antibody against a specific surface protein of target cells can be chemically cross-linked to drug-loaded cells that would direct these cells to desired cells.

Loading by lipid fusion. Lipid vesicles containing a drug can be directly fused to human erythrocytes, which lead to an exchange with a lipid-entrapped drug. This technique was used for entrapping inositol monophosphate to improve the oxygencarrying capacity of cells. However, the entrapment efficiency of this method is very low (_1%).

In vitro characterization

The in vivo performance of resealed erythrocytes is affected to a great extent by their biological properties.Hence; in vitro characterization forms an important part of studies involving such cellular carriers. -Table I: Summary of characterization parameters and their determ Parameter Method/instrument used

I. Physical characterization

Shape and surface morphology Transmission electron microscopy, scanning electron microscopy, phase contrast microscopy, optical microscopy. Vesicle size and size distribution Transmission electron microscopy, optical microscopy.Drug release Diffusion cell, dialysis

Drug content Deproteinization of cell membrane followed by assay of resealed drug, radiolabelling Surface electrical potential Zeta potential measurement Surface pH pH-sensitive probes Deformability Capillary method

II. Cellular characterization

% Hb content Deproteinization of cell membrane followed by hemoglobin assay Cell volume Laser light scattering % Cell recovery Neubaur’s chamber, hematological analyzer Osmotic fragility Stepwise incubation with isotonic to hypotonic saline solutions and determination

Of drug and hemoglobin assay Osmotic shock Dilution with distilled water and estimation

of drug and hemoglobin Turbulent shock Passage of cell suspension through 30- gauge hypodermic needle at 10 mL/min flow rate and estimation of residual drug and hemoglobin, vigorous shaking followed by hemoglobin estimation

Erythrocyte sedimentation rate ESR methods

III. Biological characterization

Sterility test Pyrogenicity Rabbit method, LAL test Animal toxicity tests

Prameters and the techniques applied for their determination. The morphology of erythrocytes decides their life span after administration. Light microscopy reveals no observable change

In resealed cells but in few cases spherical erythrocytes (spherocytes) are detected. Scanning electron microscopic studies have shown that a majority of the cells maintain their biconcave discoid shapes after the loading procedure , and few stomatocytes—a form of spherocytes with an invagination in one point—are formed. In some cases, cells of smaller size (microcyte) are also observed. Shape change (deformability) is another factor that affects the life span of the cells. This parameter evaluates the ease of passage of erythrocytes through narrow capillaries and the RES. It determines the rheological behavior of the cells and depends on the viscoelasticity of the cell membrane, viscosity of the cell contents, and the cellular surface-to-volume ratio. The deformability is measured by passage time of definite volume ofcells through capillary of 4 _m diameter or polycarbonate filter with average pore size of 45m. Another indirect approach is to evaluate chlorpromazine induced shape changes turbidimetrically .The osmotic fragility of resealed erythrocytes is an indicator of the possible changes in cell membrane integrity and the resistance of these cells to osmotic pressure of the suspension medium. The test is carried out by suspending cells in media of varying sodium chloride concentration and determining the hemoglobin released. In most cases, osmotic fragility of resealed cells is higher than that of the normal cells because of increased intracellular osmotic pressure. The turbulence fragility is yet another characteristic that depends upon changes in the integrity of cellular membrane and reflects resistance of loaded cells against hemolysis resulting from turbulent flow within circulation. It is determined by the passage of cell suspension through needles with smaller internal diameter (e.g., 30 gauge) or vigorously shaking the cell suspension . In both cases, hemoglobin and drug released after the procedure are determined. The turbulent fragility of resealed cells is found to be higher .Routine clinical hematological tests also can be carried out for drug-loaded cells, including mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin content. Studies have shown that the average size and hemoglobin content of resealed cells is lower than that of normal cells. Drug content of the cells determines the entrapment efficiency of the method used. The process involves deproteinization of packed, loaded cells (0.5 mL) with 2.0 mL acetonitrile and centrifugation at 2500 rpm for 10 min. The clear supernatant is analyzed for the drug content. The most important parameters for evaluation of resealed erythrocytes is the drug release pattern. Hemoglobin is also invariably released because drug release involves the loss of cell membrane integrity indicating hemolysis. On the basis of the various in vitro release experiments carried out on these cells, three general drug release patterns are observed:

œ the rate of drug release is considerably higher than that of hemoglobin. In other words, drug diffuses readily. Such a pattern is shown by lipophilic drugs, including methotrexate,

Phenytoin, dexamethasone, primpquin, and vitamin B12. Cell lysis is not essential for the release of such drugs.

The rate of drug release is comparable to that of hemoglobin. This indicates that cell lysis is essential for drug release and drug can not be released by mere diffusion. Polar drugs such as gentamicin, heparin, and enalaprilat, and enzymes such as asparginase peptides, including

Urogasterone and l-lysine-l-phenylalanine follow such pattern.

The rate of drug release lies between the above mentioned two extremes; for example, propranolol, isoniazid metronidazole and recombinant human erythropoietin. The two factors that determine the drug release pattern are size and polarity of the drug molecule. The release rate can be modified by cross-linking cell membrane with gluteraldehyde which results in a slower drug release. This can also be achieved by entrapping biodegradable prodrug such as o-acetyl propranolol, o-pivaloyl propranolol, cortisol-21- phosphate, prednisolone-21-sodium succinate, and cytosine arabinoside monophosphate. The complexation of a drug with macromolecules such as dextran and albumin also retard the release rate.

In vitro storage

The success of resealed erythrocytes as a drug delivery system depends to a greater extent on their in vitro storage. Preparing drug-loaded erythrocytes on a large scale and maintaining their Survival and drug content can be achieved by using suitable storage methods. However, the lack of reliable and practical storage methods has been a limiting factor for the wide-spread

Clinical use of the carrier erythrocytes. The most common storage media include Hank’s balanced salt solution and acid–citrate–dextrose at 4 _C. Cells remain viable in terms of their physiologic and carrier characteristics for at least 2 weeks at this temperature .The addition of calcium-chelating agents or the purine nucleosides improve circulation survival time of cells upon reinjection. Exposure of resealed erythrocytes to membrane stabilizing agents such as dimethyl sulfoxide, dimethyl, 3, 3-di-thio-bispropionamide, gluteraldehyde, toluene-2-4-diisocyanate followed by lyophilization or sintered glass filtration has been reported to enhance their stability upon storage. The resultant powder was stable for at least one month without any detectable changes. But the major disadvantage of this method is the presence of appreciable amount of membrane stabilizers in bound form that remarkably reduces circulation

Survival time. Other reported methods for improving storage stability include encapsulation of a prodrug that undergoes conversion to the parent drug only at body temperature, high

glycerol freezing technique, and reversible immobilization in alginate or gelatin gels .

In vivo life span

The efficacy of resealed erythrocytes is determined mainly by their survival time in circulation upon reinjection. For the purpose of sustained action, a longer life span is required, although

for delivery to target-specific RES organs, rapid phagocytosis and hence a shorter life span is desirable. The life span of resealed erythrocytes depends upon its size, shape, and surface

electrical charge as well as the extent of hemoglobin and other cell constituents lost during the loading process.The various methods used to determine in vivo survival time include labeling of cells by 51Cr or fluorescent markers such as fluorescin isothiocyanate or entrapment of 14C sucrose or gentamicin. The circulation survival kinetics of resealed erythrocytes show typical bimodal behavior with a rapid loss of cells during the first 24 h after injection, followed by a slow decline phase with a half life on the order of days or weeks. The early loss accounts for

_15–65% loss of total injected cells. The erythrocytic carriers constructed of red blood cells of

mice, cattle, pigs, dogs, sheep, goats, and monkeys exhibit a comparable circulation profile with that of normal unloaded erythrocytes. On the other hand, resealed erythrocytes prepared

from red blood cells of rabbits, chickens, and rats exhibit relatively poor circulation profile.

Applications of resealed erythrocytes

Resealed erythrocytes have several possible applications in various fields of human and veterinary medicine. Such cells could be used as circulating carriers to disseminate a drug within a prolonged period of time in circulation or in target-specific organs, including the liver, spleen, and lymph nodes. A majority of the drug delivery studies using drug-loaded erythrocytes are in the preclinical phase. In a few clinical studies, successful results were obtained.

Slow drug release. Erythrocytes have been used as circulating depots for the sustained delivery of antineoplastics, antiparasitics , veterinary antiamoebics vitamins , steroids , antibiotics and cardiovascular drugs .

The various mechanisms proposed for drug release include

œ passive diffusion

œ specialized membrane associated carrier transport

œ phagocytosis of resealed cells by macrophages of RES, subsequent accumulation of drug into the macrophage interior, followed by slow release.

œ accumulation of erythrocytes in lymph nodes upon subcutaneous administration followed by hemolysis to release the drug .

Routes of administration include intravenous, which is the most common, followed by subcutaneous, intraperitoneal, intranasal, and oral . Studies regarding the improved efficacy

of various drugs given in this form in animal models have been published. Examples include an enhancement in anti-inflammatory effect of corticosteroids in experimentally inflamed rats , increase in half life of isoniazid levothyroxine , cytosine arabinoside , and interlukin-

2 ; prolongation of plasma half life of erythropoietin from 30 min to 35 h in mice , and can increase in mean survival time of mice with experimental hepatoma after injecting methotrexate loaded erythrocytes .Thalasemic patients, because of multiple blood transfusions, are prone to hemosydrosis, a disease state associated with an excess storage of iron . This state is treated using SC or IV injections of iron-chelating compound desferrioxamine, which causes severe adverse effects in case of multiple injections. This agent was loaded on to erythrocytes and the performance of these cells upon reinjection was observed and found to be

promising. This therapeutic method is approved in the United States as regular management tool of hemosydrosis since 1984 .

Drug targeting. Ideally, drug delivery should be site-specific and target-oriented to exhibit maximal therapeutic index with minimum adverse effects. Resealed erythrocytes can act as drug carriers and targeting tools as well. Surface-modified erythrocytes are used to target organs of mononuclear phagocytic system/ reticuloendothelial system because the changes in the membrane are recognized by macrophages .However, resealed erythrocytes also can be used to target organs other than those of RES.

Targeting RES organs.Damaged erythrocytes are rapidly cleared from circulation by phagocytic Kupffer cells in liver and spleen. Resealed erythrocytes, by modifying their membranes, can therefore be used to target the liver and spleen. The various approaches to modify the surface characteristics of erythrocytes include

œ surface modification with antibodies

œ surface modification with gluteraldehyde

œ surface modification with carbohydrates such as sialic acid

œ surface modification with sulphydryl

œ surface chemical cross-linking e.g. delivery of 125I-labeled carbonic anhydrase loaded in erythrocytes cross-linked with bis (sulfosuccinimidyl) suberate and 3,3_ dithio (sulfosuccinmidyl

propionate) .

Targeting the liver. Enzyme deficiency/replacement therapy. Many

metabolic disorders related to deficient or missing enzymes can be treated by injecting these enzymes. However, the problems of exogenous enzyme therapy include a shorter circulation half life of enzymes, allergic reactions, and toxic manifestations. These problems can be successfully overcome by administering the enzymes as resealed erythrocytes. The enzymes used include _-glucosidase, _-glucoronidase, _-galactosidase .The disease caused by an accumulation of glucocerebrosidesin the liver and spleen can be treated by glucocerebrosidase-

loaded erythrocytes.

Treatment of hepatic tumors.Hepatic tumors are one of the most prevalent types of cancer. Antineoplastic drugs such as methotrexate , bleomycin , asparginase , and Adriamycin have been successfully delivered by erythrocytes. Agents such as daunorubicin diffuse rapidly from the cells upon loading and hence pose a problem. This problem can be overcome by covalently linking daunorubicin to the erythrocytic membrane using gluteraldehyde or cisaconitic acid as a spacer. The resealed erythrocytes loaded with carboplatin show localization in liver.

Treatment of parasitic diseases.The ability of resealed erythrocytes to selectively accumulate within RES organs make them useful tool during the delivery of antiparasitic agents. Parasitic diseases that involve harboring parasites in the RES organs can be successfully controlled by this method. Results were favorable in studies involving animal models for erythrocytes loaded withantimalarial , antileishmanial , and antiamoebic drugs.

Removal of RES iron overload. Desferrioxamine-loaded erythrocytes have been used to treat excess iron accumulated because of multiple transfusions to thalassemic patients. Targeting this drug to the RES is very beneficial because the aged erythrocytes are destroyed in RES organs, which results in an accumulation of iron in these organs.

Removal of toxic agents. Cannon et al. reported inhibition of cyanide intoxication with murine carrier erythrocytes containing bovine rhodanase and sodium thiosulfate. Antagonization

of organophosphorus intoxication by resealed erythrocytes containing a recombinant phosphodiestrase also has been reported.

Targeting organs other than those of RES.Recently, resealed erythrocytes have been used to target organs outside the RES. The various approaches include

œ entrapment of paramagnetic particles along with the drug

œ entrapment of photosensitive material

œ the use of ultrasound waves

œ antibody attachment to erythrocyte membrane to get specificity of action

Delivery of antiviral agents. Several reports have been cited in the literature about antiviral agents entrapped in resealed erythrocytes for effective delivery and targeting. Because most antiviral drugs are either nucleotides or nucleoside analogs, their entrapment and exit through the membrane needs careful consideration.Nucleosides are rapidly transported across the membrane whereas nucleotides are not, and thus exhibiting prolonged release profiles. The release of nucleotides requires conversion of these moieties to purine or pyrimidine bases. Resealed erythrocytes have been used to deliver deoxycytidine derivatives, recombinant herpes simplex virus type 1 (HSV-1) glycoprotein B , azidothymidine derivatives, azathioprene,

Enzyme therapy. Enzymes are widely used in clinical practice as replacement therapies to treat diseases associated with their deficiency (e.g., Gaucher’s disease, galactosuria), degradation

of toxic compounds secondary to some kind of poisoning (cyanide, organophosphorus), and as drugs. The problems involved in the direct injection of enzymes into the body have been cited. One method to overcome these problems is the use of enzyme-loaded erythrocytes. These cells then release enzymes into circulation upon hemolysis act as a “circulating bioreactors” in which substrates enter into the cell, interact with enzymes, and generate products or accumulate enzymes in RES upon hemolysis for future catalysis. The first report of successful clinical trials of the resealed erythrocytes loaded with enzymes for replacement therapy is that of _-glucoserebrosidase for the treatment of Gaucher’s disease.The disease is characterized by inborn deficiency of lysosomal -glucoserebrosidase in cells of RES thereby leading to accumulation of _-glucoserebrosides in macrophages of the RES. To treat lead poisoning, the concentration of _-aminolevulinate dehydrogenase (ALA-D) in erythrocytes decreases. This

leads to an accumulation of _-aminolevulinic acid in tissues, blood, and urine. This state leads to acute porphyria and CNSrelated problems. An injection of resealed erythrocytes Other enzymes used for loading resealed erythrocytes include

Improvement in oxygen delivery to tissues. Hemoglobin is the protein responsible for the oxygen-carrying capacity of erythrocytes. Under normal conditions, 95% of hemoglobin is saturated with oxygen in the lungs, whereas under physiologic conditions in peripheral blood stream only _25% of oxygenated hemoglobin becomes deoxygenated. Thus, the major fraction

of oxygen bound to hemoglobin is recirculated with venous blood to the lungs. The use of this bound fraction has been suggested for the treatment of oxygen deficiency. 2,3 Diphosphoglycerate (2,3-DPG) is a natural effector of hemoglobin. The binding affinity of hemoglobin for oxygen changes reversibly with changes in intracellular concentration of 2,3-DPG. This compensates for changes in the oxygen pressure outside of the body, as the affinity of 2,3-DPG to oxygen is much higher than that of hemoglobin. Other organic polyphosphates can serve as allosteric effectors of hemoglobin with binding affinities higher than those of 2,3-DPG and can compete with 2,3-DPG for binding to hemoglobin. Inositol hexophosphate (IHP) is one of the strongest effectors of this type. However, because of its ionization at physiologic pH, it cannot enter erythrocytes. Hence, it is entrapped by the electroporation process. Upon encapsulation, IHP irreversibly binds to hemoglobin, thereby decreasing the oxygen affinity to hemoglobin and subsequent shift of oxygen binding isotherm to the right. As a result, the oxygen pressure corresponding to 50% of the total binding capacity of hemoglobin to oxygen (P50 value) increases from 26–27 mm Hg to _50 mm Hg.In the presence of IHP encapsulated in erythrocytes, the difference between the oxygen bound fraction of hemoglobin in lungs and tissues increases, thereby increasing the oxygen concentration in tissues. Also, the extent of carbamate formed in the N-terminal amine group of _chain of hemoglobin decreases, which is compensated by an uptake of H_ and CO2 that leads to increased formation of bicarbonate ion. IV injection of IHP-loaded erythrocytes to piglets led to a decrease in cardiac output with a constant oxygen consumption by animals. This indicates that because of an increased extraction ratio of oxygen by tissues, a given amount of oxygen can be delivered in lower blood flow. In addition, these erythrocytes reduce ejection fraction, left ventricular diastolic volume, and heart rate.An isolated perfused-heart model showed reduction in coronary blood flow with increased oxygen consumption by myocardium upon administration of IHP-loaded erythrocytes. The same results are reported when intact animal models were use. An application of IHP-loaded erythrocytes for improved oxygensupply is beneficial under the following conditions:

œ high altitude conditions where the partial pressure of oxygen is low

œ reduction in the number of alveoli, where exchange surface of the lungs is decreased

œ increased resistance to oxygen diffusion in the lungs

œ reduction in oxygen transport capacity

œ mutation or chemical modification, which involves a decrease in oxygen affinity for hemoglobin

œ increased radiosensitivity of radiation-sensitive tumors

œ restoration of oxygen-delivery capacity of stored blood

œ ischemia of myocardium, brain, or other tissues.

Microinjection of macromolecules

Biological functions of macromolecules such as DNA,RNA, and proteins are exploited for various cell biological applications. Hence, various methods are used to entrap these macromolecules

Into cultured cells (e.g., microinjection). A relatively simple structure and a lack of complex cellular components (e.g., nucleus) in erythrocytes make them good candidates for the entrapment of macromolecules. In microinjection, erythrocytes are used as microsyringes for injection to the host cells. The microinjection process involves culturing host eukaryotic cells in vitro. The cells are coated with fusogenic agent and then suspended with erythrocytes loaded with the compound of interest in an isotonic medium. Sendai virus (hemagglutinating virus of Japan, HVJ) or its glycoproteins or polyethylene glycol have been used as fusogenic agents. The

fusogen causes fusion of cosuspended erythrocytes and eukaryotic cells. Thus, the contents of resealed erythrocytes and the compound of interest are transferred to host cell. This procedure

has been used to microinject DNA fragments, arginase, proteins, nucleic acids, ferritin, latex particles, bovine and human serum albumin, and enzyme thymidine kinase to various eukaryotic cells. Advantages of this method include quantitative injection of materials into cells, simultaneous introduction of several materials into a large number of cells, minimal damage to the cell, avoidance of degradation effects of lysosomal enzymes, and simplicity of the technique. Disadvantages include a need for a larger size of fused cells, thus making them amenable to RES clearance, adverse effects of fusogens, and unpredictable effects on cell resulting from the co introduction of various components. Hence, this method is limited to mainly cell biological applications rather than drug delivery.

Novel approaches

Erythrosomes. These are specially engineered vesicular systems that are chemically cross-linked to human erythrocytes’ support upon which a lipid bilayer is coated. This process is achieved by modifying a reverse-phase evaporation technique. These vesicles have been proposed as useful encapsulation systems for macromolecular drugs.

Nanoerythrosomes. These are prepared by extrusion of erythrocyte ghosts to produce small vesicles with an average diameter of 100 nm. Daunorubicin was covalently conjugated to

nanoerythrosomes using gluteraldehyde spacer. This complex was more active than free daunorubicin alone, both in vitro and in vivo.

References

1. D.A. Lewis and H.O. Alpar, “Therapeutic Possibilities of Drugs Encapsulated

in Erythrocytes,” Int. J. Pharm. 22, 137–146 (1984).

2. U. Zimmermann, Cellular Drug-Carrier Systems and Their Possible

Targeting In Targeted Drugs, EP Goldberg, Ed. (John Wiley & Sons,

New York, 1983), pp. 153–200.

3. S. Jain and N.K. Jain, “Engineered Erythrocytes as a Drug Delivery

System,” Indian J. Pharm. Sci. 59, 275–281 (1997).

4. S.P. Vyas and R.K. Khar, Resealed Erythrocytes in Targeted and Controlled

Drug Delivery: Novel Carrier Systems (CBS Publishers and Distributors,

India, 2002), pp. 87–416.

5. R. Baker, “Entry of Ferritin Into Human Red Cells During Hypotonic

Hemolysis,” Nature 215, 424–425 (1967).

6. G.J. Torotra and S.R. Grabowski, “The Cardiovascular System: The

Blood,” in Principles of Anatomy and Physiology (Harper Collins College

Publishers, New York, NY, 7th ed., 1993), pp. 566–590.

(1987).

7.S.P. Vyas and V.K. Dixit, Pharmaceutical Biotechnology 1 (CBS Publishers

& Distributors, New Delhi, 1999), pp. 655.

niper question paper

2010-11-13T11:01:00.000-08:00

NIPER -2006 (QUETION PAPER)

NOTE: - The paper is not the clone of original paper, but it has been prepared by us after

coming out of exam hall by recalling the questions, and by help of many students.

Some questions are reproduced as they are and some in fragments.

The main objective behind this work of preparing this rough format is to pass the information

about the exam to the next aspirants of NIPER, as the syllabus of the exam is not declared. The

word in bracket indicates answer for that question.

Time- 2 hr. Marks-

100

Qutions-200. Negative marking-@25%

Format-objective type (with 4 options)

Answers-to be marked on ORS SHEET with HB pencil.

1. Mode of action of taxol

2. Cyclodextrin (which form is more soluble)

3. Bigesst cotton producing country.

4. Alanine configuration(R or S)

5. Correct structure of nifedipine

6. Which amongst following is Ca channel blocker.

7. Glutathione is (ans-tripeptide and detoxifing agent)

8. Polypharmacy means-

9. Phenytoin –therapeutic use

10. Propranolol contradicted in-

11. Which amongst following undergo more first pass metabolism (propranolol, digitalis,

aspirin).

12. Calculate %age yield (given therotical and practical yield)

13. Term 'IPEP' is related with-

14. Paracetamol (toxic metabolite)

15. Benzyl alcohol in parenteral concentration (how much?)

16. Area of rectangle (given length, bredth in terms of length)

17. Interest calculation

18. Deadly organism of malaria (Plasmodium Falcipuram)

19. Which of following is cardiotoxic.

20. Antonym of solisitarious-

21. Synonym of macabre

22. Coumarin ring system-scientific name

23. Ca channels in heart are of which type (ans-voltage gated)

24. Receptors are – (protein in nature)

25. Serotonin-is (ans –neurotransmitter)

26. Second messenger system – calcium - cAMP - cGMP - all the above.

28. In cough syrup alkaloid present (ans-codeine)

29. Aspirin MOA

30. Drug for alopecia (Minoxidil)

31. Protogenic solvent – water - acetic acid - CCl4 - None.

32. Which one is optically active eg. allens

33. Enalapril

34. Drug used in Parkinsonism

35. Tretment agent for cerebral malaria

36. Primaquin use (specific)

37. Intestinal amoebiasis causative agent.

38. Dopamine agonist- (Bromocriptine)

39. ACE inhibitors side effect.

40. Statins use- (Hypolipidemic agents)

41. Prostaglandin synthesis which enzymes involved.

42. Rifampicin use other than T.B.

43. L-threose and L-erythrose are

44. Marine anticancer drug

45. Fermentation-batch process

46. Which of following is not static dryer? (Tunnel dryer)

47. Podophyllotoxin is (lignan)

48. Betain-structure

49. Gene _expression is done by(transcription)

50. DNA is present in-

51. Ring analogues of sugar are called (anomers)

52. Crystallization of sugar in syrup is avoided by addition of

- Alcohol

- Lemon juice

53. Application of head space analysis

54. Bacterial cell wall constitution

55. Cellular structure is identified by (phase contrast microscopy)

- Electron Microscopy

- Phase contrast Microscopy

- Dark Field Microscopy

- None

56. Metals and metalloids are identified by which spectroscopy-

57. Phosphorescence and fluorescence (emission spectroscopy)

58. Energy wise order-UV, IR, NMR

59. Spectroscopy for detection of hydrogen bonding (IR)

60. COCl- IR stretching range

61 Lactum rings- IR stretching range

62 Fluid energy mill- particle size? (10-30 µm)

63. If pKa of drug is 5.4 maximum absorption will occur from-

- Stomach

- Duodenum

- Small intestine

- Large intestine

64. Morphine mainly acts on (µ receptor)

-µ receptor

-µ and delta receptor

-delta and kappa receptor

-kappa receptor

65. Anti acetylcholine used in peptic ulcer-

66. Metachlopromide-MOA

67 Agent used in treatment of anticancer agent induced emesis (ondencetron)

68 Gallic acid is-antioxidant, preservative,…,none of the above.

69. Eye drops differ from parenteral preparation (pyrogenicity)

- Sterility

- Particulate matter

- Pyrogenicity

- Isotonicity

70. Agent used in treatment of acute gout. (colchicin)

71 000 capsule capacity in mg.

72. Green bones are used for preparation of which type of gelatin.

73. HIV is caused by

74. Name of scientist-meningitis discovery

75. Equation related with osmosis

76 If hour hand of a clock at 12noon is at north east, then at 1pm where will be the hour hand of

the clock-----east, west, north, south?

77. Dipole moment in 1,2-dibromoethane

78. B.S of Indian Ginseng

79. Alzheimer's disease is (neuro degenerative disease)

80. CVS drug- which neutraceutical

81. Circular dichroism—application

82. Absorptivity or extinction coefficient depends upon---

83. In mono substituted cyclohexane, which form is stable – axial, equatorial

84. Tamoxifen is (estrogen antagonist)

85. Triterpines are prepared from (six isoprene unit)

86. Terpenes biosynthetic pathway

87. Indole alkaloids r biosynthesized from (Tryptophan)

88. Modern chemotherapy was discovered by

89. Bacteria r present in following except------- ice, sea water, distilled water, soil

90. Submerged culture is difficult for which micro organism.

91. Mammalian cell gene _expression is done by (protein synthesis)

92. Which packaging material is more water vapour permeable?

93 Vehicle for soft gelatin capsule

94. Material used for packaging during Accelerated stability studies.

95. Polymers are added to amorphous substances for what?

96. HLB range of w/o emulsion

97. Which of the following is directly titrated with acid----------

- Aminop- Phenytoin,

- Sulphynpyrazone,

- Phenobarbitone.

98. Formula for angle of repose

99. ABC concept is used for (Inventory Control)

100. Liposomes are used to solubilize

101. Nujol is (mineral oil)

102. Detector used in IR

103. IR source

104. Range of UV-visible light

105. Reference substance used in NMR

106. Diosgenin has which basic nucleus?

107. When IND is applied?

108. When phase IV clinical trials are started

109. Enthalpy is (heat content)

110. Kinetics is study of -----rate, order, molecular, none of above

111. Which one is optically active—crystal, molecule-----

112. Structure of antibody

113. Which one is reducing sugar (sucrose)

114. Endogenous anticoagulant (heparin)

115. Insulin is secreted by

116. Omeprazole MOA

117. pH of 0.05 M HCl is

118. Metronidazole use

119. Different polymorphs differ in which properties

120. Albuterol MOA

121. Salmeterol which class

122. Selective alpha 1 receptor antagonist (Prazosin)

123. Fatal Adverse effect is of which combination

- Terfenedine + loratidine

- Terfenedine + erythromycin

124. Dissolution test apparatus for tablets

- USP I/ II

125. Calibration of IR – solvent used?

127. What will happen when heat is increased for exothermic reaction? (reaction will

shift to which side?)

128. For spontaneous reaction free energy is- ----- +ve , —ve

129. Mass spectroscopy--- Base peak?

130. Splitting in 1,4 dioxane

131. Carbonic unhydrase inhibirors (Acetazolamide)

132. Phenolphthalein is... (acid base indicator)

133. Microvilli in intestine ---the function is.

134. RS is what as per IP

135. 1, 3 cyclohexane which form is optically active?

136. HPLC ---widely used (Reversed phase)

137. Size exclusion chromatography use..hyllin,

138. A + B = 102; A — B = 24 what is A

139. 1:9:17:33:49:73:?

140. Delirium tremors which drug is used …

141. Which color pigment present in tomato (lycopene)

142. Which vitamin in high dose causes teratogenicity? (Vit. A)

143. Cytokines are (proteins)

144. NMR signal is expressed in (ppm)

145. Nuclear receptor

146. 2 amide bonds are present in (tripeptide)

147. What causes serine hydrolysis?

148. Non aqueous system – binder used? (Ethyl Cellulose)

149. Saffron is cultivated in which state? (Kashmir)

150. Welfare state means….

151. Back titration is done for ……….

152. Sparingly soluble means…(30 to 100 parts)

153. Which polymer is more permeable to water- vapour?

154. Terfenedine side effect?

155. Myasthenia Gravis is caused due to..

156. Nicotinic receptors are (ligand gated)

157. Number of double bonds are determined by …

- H2

- Br2

- Ozonolysis

- all the above

158. The compounds which are not detected by UV detector are detected by

- Derivitization

- Mass spectrometry

- Electrochemical detector - all the above

159. Neostigmine does not cross BBB because it is (polar)

160. Which drugs cross BBB? (lipophilic)

161. Effect of Muscarinic drugs on Gastric secretion….

162. Which of the following port has free trade?

- Cochin

- Madras

- Kalanda

- Tutikotin

163. Hemoglobin carries -------

- Oxygen

- Co2

- Oxygen and Co2.

- None of the above

164. Significance of iodine value

165. t-RNA structural component

166. Carbene is formed in which reaction? (E1CB)

167. What is Bredt rule?

168. Polymer's role

169. Which of the following inhibits enzyme induction?

170. CH3Cl in NMR what is effect of Cl? (causes deshielding and down filled effect)

171. Auxochrome enhances…(absorption)

PHARMACEUTICAL EDUCATION

NIPER JEE 2011 paper

estimation of multi-component formulations

Spectrophotometric multi-component analysis

Simultaneous equation method (Vierodt’s method) 3

Two wavelength method3

The absorption ratio method3

Geometric correction method3

Absorption factor method (Absorption correction method) 3

Orthogonal polynomial method3

Difference spectrophotometry3

Derivative spectrophotometry3

Area under curve method4

High performance liquid chromatography (HPLC):

High performance thin layer chromatography (HPTLC):

Gas chromatography (GC):

Validation of methods6:

Biopharmaceutical Classification Of Drugs

Biopharmaceutical Classification System:

Applications of BCS in oral drug delivery technology (5):

Conclusion:

References:

USP Minimum Sample Weight

Comparison of Matrix Effects in HPLC-MS/MS

NIPER question paper 2009

effect of cancer chemotherapy on reproduction and sexuality

Over-the-counter drug

ADVANTAGES AND DISADVANTAGES OF HPLC

polymeric nanoparticles as drug carrier

9.1 Recent Developments in Polymeric Nanoparticle Engineering and Their Applications in experimental and Clinical Oncology

niosome

a.) Ether injection method-

b.) Hand shaking method (Thin film hydration technique)-

c.) Sonication-

d.) Micro fluidization-

f.) Reverse Phase Evaporation Technique (REV)-

g.)Trans membrane pH gradient (inside acidic) Drug Uptake Process (remote Loading)-

h.) The "Bubble" Method-

i.) Formation of niosomes from proniosomes-

5.1.Separation of Unentrapped Drug:-

e.) Entrapment efficiency-

f.) Vesicle diameter-

g.) In-vitro release-

6.Applications-

1) Targeting of bioactive agents-

a) To reticulo-endothelial system (RES)

b) To organs other than RES

2) Neoplasia-

3) Leishmaniasis-

4) Delivery of peptide drugs-

5) Immunological application of niosomes-

6) Niosomes as carriers for Hemoglobin-

7) Transdermal delivery of drugs by niosomes-

8) Other Applications-

a) Sustained Release

b) Localized Drug Action

8. Recent development / future advancement:-

9. References:-

Herb–drug interactions: an overview of the clinical evidence

pharma job cover letter new

sample cover letter for pharma jobs

High performance liquid chromatography

tablet, capsule and ORS production and quality control test

natural polymer

PART 2 SURFACE MODIFICATION AND BIOMIMETIC COATINGS

PART 3 BIODEGRADABLE SCAFFOLDS FOR TISSUE REGENERATION

PART 4 NATURALLY-DERIVED HYDROGENS: FUNDAMENTALS, CHALLENGES AND APPLICATIONS IN TISSUE ENGINEERING AND REGENERATIVE MEDICINE

PART 5 SYSTEMS FOR THE SUSTAINED RELEASE OF MOLECULES

PART 6 BIOCOMPATIBILITY OF NATURAL-BASED POLYMERS

Types of Natural Polymers

Examples for Natural Polymer

Types of Natural Polymer

pharmacology mnemonics for easy memorizing

emergency drugs pneumonics

pharmacology pneumonic

resealed erythrocytes

niper question paper

Simultaneous equation method (Vierodt’s method)³

Two wavelength method³

The absorption ratio method³

Geometric correction method³

Absorption factor method (Absorption correction method)³

Orthogonal polynomial method³

Difference spectrophotometry³

Derivative spectrophotometry³

Area under curve method⁴

Validation of methods⁶: