Xarelto (rivaroxaban); Janssen Pharmaceuticals; For the reduction in the risk of stroke and systemic embolism resulting from atrial fibrillation, Approved November 2011
Dermatology/Plastic Surgery
Firazyr (icatibant); Shire; For the treatment of acute attacks of hereditary angioedema, Approved August of 2011
laViv (azficel–T); Fibrocell Science; For the improvement of nasolabial fold wrinkles in adults, Approved June 2011
Endocrinology
Tradjenta (linagliptin); Boehringer Ingelheim; For the treatment of type II diabetes, Approved May 2011
Gastroenterology
Dificid (fidaxomicin); Optimer Pharmaceuticals; For the treatment of Clostridium difficile-associated diarrhea, Approved May 2011
Incivek (telaprevir); Vertex; For the treatment of genotype 1 chronic hepatitis C, Approved May 2011
Victrelis (boceprevir); Merck; For the treatment of chronic hepatitis C genotype 1, Approved May 2011
The Parliamentary Standing Committee on Health and Family Welfare also pointed to serious lapses and irregularities on the approvals of new drugs and pointed out that 33 such drugs were approved without conducting clinical trials on Indian patients.
The Committee said scrutiny of 42 drugs picked up randomly involving grant of drug approvals in utter disregard of regulatory procedures and violation of rules and pointed out to files of approval of three controversial drugs (pefloxacin, lomefloxacin and sparfloxacin) found missing and untraceable.
These drugs were either never marketed or withdrawn in the US, Canada, Britain, Australia and other countries.
Citing the example of Deanxit, the Panel pointed out that the drug continued to be prohibited for sale and use in Denmark, the country of its origin, and thus permission to import and market it in India was given unlawfully.The panel cited another example of Letrozole by Novartis, used as an anti-cancer drugs used only in post-menopausal women, is used only in India where it is permitted for use in female infertility.
1. Amidopyrine 2. Phenacetin 3. Nialamide 4. Methaqualone 5. Methapyriline (and its salts) 6. Practolol 7. Penicillin skin/eye ointment 8. Tetracycline/Oxytetracyline/Demeclocycline liquid oral preparations. 9. Chloral hydrate 10. Dover’s powder and Dover’s powder tablets I.P. 11. Chloroform exceeding 0.5% w/w or v/v in pharmaceutical preparations. 12. Mepacrine HCl (Quinacrine and its salts) in any dosage form for use for female sterilization or contraception. 13. Fenfluramine 14. Dexfenfluramine 15. Terfenadine 16. Astemizole 17. Phenformin 18. Rofecoxib 19. Valdecoxib 20. Rosiglitazone 21. Nimesulide Formulatios In Children Below The Age Of 12 years 22. Cisapride 23. Rimonabant 24. Phenyl Propanolamine 25. Human Placenta Extract in topical application for wound healing and injection for pelvic inflammatory diseases. 26. Sibutramine 27. R-Sibutramine 28. Gatifloxacin 29. Tegaserod
B. Fixed dose combination with any other drug
1. Corticosteroids with any other drug for internal use. 2. Chloramphenicol with any other drug for internal use. 3. Sodium bromide/chloral hydrate with other drugs. 4. Ergot with any drug except preparations containing ergotamine, caffeine, analgesics, antihistamines for treatment of migraine. 5. Anabolic steroids with other drugs. 6. Metoclopramide with other drugs (except with aspirin/paracetamol). 7. Pectin and/or kaolin with any drug which is systematically absorbed from g.i. tract, except for combination of pectin and/or kaolin with drugs not systematically absorbed. 8. Hydroxyquinolines with any other drug except in preparations for external use. 9. Oxyphenbutazone or phenylbutazone with any other drug. 10. Dextropropoxyphene with any other drug except antispasmodics and/or NSAIDs. 11. Analgin (metamizol) with any other drug.
1. Penicillins with Sulfonamides. 2. Tetracyclines with Vitamin C 3. Antitubercular drugs with Vitamins (except Isoniazid with Pyridoxine HCl). 4. Vitamins with Analgesics/Antiinflammatory drugs. 5. Vitamins with Tranquillisers. 6. Atropine and Analgesic-antipyretics. 7. Yohimbine and Strychnine with Testosterone and Vitamins. 8. Strychnine and Caffeine in tonics. 9. Iron with Strychnine, Arsenic and Yohimbine. 10. Antihistaminics with Antidiarrhoeals. 11. More than one Antihistamine in the same preparation. 12. Sedatives/Hypnotics/Anxiolytics with Analgesic-antipyretics. 13. H2 receptor antagonists with Antacids (except those combinations approved by Drugs Controller, India). 14. Anthelmintics (except Piperazine) with a Cathartic/Purgative. 15. Salbutamol (or any other bronchodilator) with centrally acting Antitussive and/or an Antihistamine. 16. Centrally acting Antitussives with Antihistamines having atropine like activity in expectorants. 17. Centrally acting Antitussive and/or Antihistamine in preparations for cough associated with asthma. 18. Laxative and/or antispasmodic drugs in enzyme preparations. 19. Glycerophosphates and/or other phosphates and/or CNS stimulant in liquid oral tonics. 20. Estrogen and Progestin (other than oral contraceptives) containing per tablet Estrogen more than 50 ug ethinylestradiol (or equivalent) and progestin more than 3 mg of norethisterone acetate (or equivalent) and, all fixed dose combination injectable preparations containing synthetic estrogen and progesterone. 21. Ethambutol with Isoniazid, except in the following daily doses: Isoniazid 200 mg + Ethambutol 600 mg or Isoniaizd 300 mg + Ethambutol 800 mg 22. Pyrazinamide with other antitubercular drugs, except that which provide the following daily doses. Rifampicin 450 to 600 mg Isoniazid 300 to 400 mg Pyrazinamide 1000 to 1500 mg 23. Essential oils with Alcohol having percentage higher than 20% proof (except preparations given in the I.P.). 24. Liquid oral tonic preparations containing alcohol more than 20% proof. 25. Streptomycin with penicillin in parenteral preparation. 26. Antidiarrhoeals containing adsorbants like kaolin, pectin, attapulgite, activated charcoal etc. 27. Antidiarrhoeals containing phthalylsulfathiazole, succinyl sulfathiazole, sulfaguanidine, neomycin, streptomycin, dihydrostreptomycin. 28. Antidiarrhoeal formulations for pediatric use containing diphenoxylate, loperamide, atropine, hyoscyamine, halogenated hydroxyquionolines. 29. Antidiarrhoeals with electrolytes. 30. Fixed dose combinations of haemoglobin in any form. 31. Pancreatine or pancrelipase containing amylase, protease and lipase with any other enzyme. 32. Oral rehydration salts other than those conforming to the following parameters: a) Oral rehydration salts on reconstitution to one litre shall contain: sodium-50 to 90 mM; total osmolarity-240 to 290 mOsm; dextrose: sodium molar ratio-not less than 1:1 and not more than 3:1. b) Cereal based ORS on reconstitution to one litre shall contain: total osmolarity not more than 2900 mOsm. Precooked rice equivalent to not less than 50 g and not more than 80 g as total replacement of dextrose. c) ORS may contain amino acids in addition to ORS conforming to the parameters specified above and labeled with the indication for “Adult Choleratic Diarrhoea” only. d) ORS shall not contain mono or polysaccharides or saccharin sweetening agent. 33. A drug, standards of which are prescribed in the 2nd schedule to Drugs and Cosmetics Act with an Ayurvedic Siddha or Unani drug. 34. Vitamin B1, Vit B6 and Vit B12 for human use. 35. Diazepam with diphenhydramine HCl. 36. Nitrofurantoin with Trimethoprim. 37. Phenobarbitone with any antiasthmatic drug, or with hyoscine and/or Hyoscyamine, or ergotamine and/or belladonna. 38. Haloperidol with any anticholinergic agent including propantheline Br. 39. Nalidixic acid with any antiamoebic including metronidazole. 40. Loperamide with furazolidone. 41. Cyproheptadine with lysine or peptone. 42. Diazepam and Diphenhyhydramine Hydrochloride.
f hypoxia, or low oxygen levels in cells, is proven to be a key driver of certain types of cancer, treatment plans for curing the malignant growth can change in significant ways, said Ying Xu, professor of bioinformatics and computational biology at Georgia University’s Franklin College of Arts and Sciences.
The research team analysed samples of messenger RNA data, also called transcriptomic data, from seven different cancer types in a publicly available database.
They found that long-term lack of oxygen in cells may be a key driver of cancer growth, the Journal of Molecular Cell Biology reports.
Previous studies had linked low oxygen levels in cells as a contributing factor in cancer development, but not as the driving force for cancer growth.
High cancer rates worldwide cannot be explained by chance genetic mutations alone, Xu said, according to a Georgia statement.
He added that bioinformatics, which melds biology and computational science, has allowed researchers to see cancer in a new light.
“Cancer drugs try to get to the root, at the molecular level, of a particular mutation, but the cancer often bypasses it,” Xu said.
“So we think that possibly, genetic mutations may not be the main driver of cancer.”
The researchers analysed data downloaded from the Stanford Microarray database via a software programme to detect abnormal gene expression patterns in seven cancers: breast, kidney, liver, lung, ovary, pancreatic and stomach.
Xu relied on the gene HIF1A as a biomarker of the amount of molecular oxygen in a cell. All seven cancers showed increasing amounts of HIF1A, indicating decreasing oxygen levels in the cancer cells.
Low oxygen levels in a cell interrupt the activity of oxidative phosphorylation, a term for the highly efficient way that cells normally use to convert food to energy.
Low oxygen levels engender the process of creating new blood vessels. They provide fresh oxygen, thus improving oxygen levels in the cell and tumour and slowing the cancer growth – but only temporarily.
“When a cancer cell gets more food, it grows; this makes the tumour biomass bigger and even more hypoxic. In turn, the energy-conversion efficiency goes further down, making the cells even hungrier and triggering the cells to get more food from blood circulation, creating a vicious cycle. This could be a key driver of cancer,” Xu said.
The U.S. Food and Drug Administration issued its final rule on sterility testing, amending the requirements for most licensed biological products. The action follows a retrospective review of agency regulations to promote improvement and innovation and is in response to Executive Order 13563 that is designed to improve regulation and regulatory review.
The FDA recognizes the role innovation plays in bringing safe and effective products to market in a timely and cost-efficient manner. This action reflects the agency’s efforts to review and, as necessary, update biologics regulations, to keep pace with technological developments and to boost regulatory science.
The amendments to the sterility testing rule will provide manufacturers of biological products the flexibility, as appropriate, to keep pace with technological and scientific advances.
FDA issued a final rule on sterility testing on May 3, 2012, that amends the requirements for most licensed biological products and aims to provide manufacturers with the flexibility, as appropriate, to keep pace with technological and scientific advances. The rule is in response to President Obama’s Executive Order 13563 which called for improving regulation and regulatory review.
Specifically, the rule revises sterility requirements under Title 21 of the Code of Federal Regulations (CFR), subchapter F, parts 600 through 680 as follows:
“Eliminates specified sterility test methods, culture media formulae (or formulation), and culture media test requirements
Eliminates specified membrane filtration procedure requirements for certain products
Eliminates specified sterility test requirements for most bulk material
Modifies the repeat sterility test requirements, so that repeat tests will occur only once for each lot
Replaces the storage and maintenance requirements for cultures of test organisms used to determine the “growth-promoting qualities” of culture media with validation requirements specifying that any sterility test used is able to consistently detect the presence of viable contaminating microorganisms, and with verification of “growth-promoting properties” or microorganism-detection capabilities of test and test components
Replaces the sample size or amount requirement with a requirement that the sample be appropriate to the material being tested
Replaces the Interpretation of test results section under § 610.12(c) with a requirement that manufacturers establish, implement, and follow written procedures for sterility testing that describe, at a minimum, the test method used, the method of sampling, and the written specifications for acceptance or rejection of each lot
Simplifies and clarifies the Exceptions section under § 610.12(h)
Identifies the Director of CDER as one of the two Center directors authorized to grant an exemption under the exception provision at § 610.12(h)(2). In the proposed rule, the Center for Devices and Radiological Health was erroneously identified in this exception, instead of the Center for Drug Evaluation and Research
Revises the definition of the term “sterility” under § 600.3(q).
Eliminates certain exceptions for allergenic products related to sterility testing under § 680.3(c).”
Companies will not have long to implement the changes as the rule takes effect June 4, 2012. The proposed rule received several comments from industry and the final rule includes the agency’s response to those recommendations. Overall, FDA “recognizes the role innovation plays in bringing safe and effective products to market in a timely and cost-efficient manner,” according to an FDA announcement of the rule. “This action reflects the agency’s efforts to review and, as necessary, update biologics regulations, to keep pace with technological developments and to boost regulatory science.”
MONOPHASIC LIQUID DOSAGE FORM Syllabus Definition and account of oral solutions, syrups and elixirs.
Their importance in the Medical field.
Components of the formulations with examples: Solvents, buffers, sweeteners, acidifiers, flavors, and preservatives.
Development of the formula.
Preparation , equipment in industrial scale.
Solution In pharmaceutical terms, solutions are liquid preparations that contains one or more chemical substances dissolved in a suitable solvent or mixture of mutually miscible solvents. Classification of solution (i) According to the route of administration
a) Oral solutions—through oral route.
b) Otic solutions—instilled in the ears.
c) Ophthalmic solution—instilled in the eyes.
d) Topical solutions—applied over the skin surface. (ii) According to composition and uses a) Syrup—aqueous solution containing sugar.
b) Elixir—sweetened hydroalcoholic (combination of water and ethanol) solution.
c) Spirit—Solution of aromatic materials in alcohol.
d) Aromatic Water—Solution of aromatic material in water.
e) Tincture / Fluid extract—Solution prepared by extracting active constituents from crude drugs. e.g. Compound cardamom tincture. They may also be solutions of chemical substances dissolved in alcohol or in hydroalcoholic solvent. e.g. Tincture of Iodine.
f) Injection—Certain solution prepared to be sterile and pyrogen-free and intended for parenteral administration.
Formulation Consideration 1) Solubility a) pH
b) Cosolvency
c) Solubilization
d) Complexation
e) Hydrotrophy
f) Chemical modification of the drug molecule 2) Preservation a) Preservatives
b) Antioxidants
c) Reducing agents
d) Synergists 3) Organoleptic consideration a) Sweetening agents
b) Flavoring agents
c) Coloring agents
d) Viscosity control
e) Overall appearance
4) Stability a) Chemical stability
b) Physical stability
SOLUBILITY When a solid solute is dissolved in a liquid solvent two types of interactions are evident—one is the intra-molecular force between the solute molecules and the other is the intermolecular force between the solute and solvent molecules. When a solute dissolves, the substance’s intra-molecular forces (cohesive force) must be overcome by the force of attraction between the solute and solvent molecules (adhesive force).This involves breaking the solute-solute forces and the solvent-solvent forces to achieve the solute-solvent forces attraction.
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[like-gate] Expression of solubility According to Indian Pharmacopoeia Descriptive Phrase———-Approximate quantities(ml) of solvent by volume for 1 part (1 gm) of solute by weight
Very soluble——————–less than 1 part
Freely soluble ——————from 1 to 10 parts
Soluble————————-from 10 to 30 parts
Sparingly soluble—————from 30 to 100 parts
Slightly soluble—————–from 100 to 1000 parts
Very slightly soluble————from 1000 to 10,000 parts
Practically insoluble———–more than 10,000 parts
Solubility The solubility of an agent in a particular solvent indicates the maximum concentration to which a solution may be prepared with that agent and that solvent.
Determination of Equilibrium Solubility of a Drug
An excess of the drug ( finely powdered to minimize the time required to attain the equilibrium) is placed in a vial along with a specific amount of the solvent. The tightly closed vial is then agitated at constant temperatures (preferably at temperature somewhat higher than room temperature e.g. 300C so that constant conditions can be maintained regardless of normal laboratory temperature variations), and the amount of drug in solution is determined periodically by assay (by some chemical method) of a filtered sample of the supernate. Equilibrium is not achieved until at least two successive samplings give the same result.
The solubility is generally expressed in mg of solute per ml of solvent at 250 C or per 100 ml etc.
Solubility of a drug depends on temperature, solvent, pH and the chemical nature of the molecule itself. By modifying these parameters the solubility of a drug can be manipulated according to the requirement of designing the dosage form. pH A large number of drugs are either weak acids or weak bases. The solubility of these agents can be markedly influenced by the pH of the environment. When a weakly acidic drug is dissolved in water it can remain in three states, namely undissolved, dissolved and ionized which can be expressed in the following reaction format:
DH SOLID (UNDISSOLVED) <—–> DH (SOLUTIONS) (UN DISSOCIATED) <——> D
MINUS (DISSOCIATED/ IONIZED) + H PLUS PROTON
The relationship between equilibrium solubility of a weakly acidic drug and the pH of the environment can be expressed by Henderson-Hasselbach equation:
PH = pKa+ log( D – )/log (DH)
where pKa = Dissociation constant of the acid
[D-] = Molar concentration of ionized drug
[DH] = Molar concentration of unionized drug
The same equation can be written in the following forms:
PH = pKa + log (ionized)/(un ionized)
PH = pKa + log ( base )/( acid)
where DH = Acid
D- = Corresponding base of the acid (DH) Weak Acid DH SOLID <—-> DH SOLUTION-DISSOLVED,UN IONISED <——> D- + H+
PH =pKa + log D- / DH
pH = pKa + log (ionised ) /(un ionised)
pH = pKa + log (base) / (acid) Weak Base pH =pKa+ log (DOH-)/ (D+)
pH=pKa +log (unionised) / (ionised)
pH = pKa+ log( base )/(acid)
DH = acid
D – = corresponding base of DH
DOH = base
D+ = corresponding acid of the base DOH
To maintain the drug in soluble state the solution of a drug must be done in a suitable buffer solution. The buffer must have the following properties:
1. The buffer must have adequate capacity in the desired pH range.
2. The buffer must be biologically safe for the intended use.
3. The buffer (or its pH range) must have minimum interference on the stability of the final product.
4. The buffer should permit acceptable flavoring and coloring of the product.
e.g. Some commonly used buffer systems are ammonium chloride, diethanol amine, triethanolamine, boric acid, carbonic acid, phosphate buffer, glutamic acid, tartaric acid, citric acid buffer, acetic acid buffer etc.
COSOLVENCY
Weak electrolytes and nonpolar molecules frequently have poor water solubility. These types of solutes are more soluble in a mixture of solvents than in one solvent alone. This phenomenon is known as cosolvency; and the solvents that, in combination increases the solubility of the solute are called cosolvents.
To increase the water solubility of a drug another water miscible solvent in which the drug has good solubility is mixed. Mechanism of action It has been proposed that a cosolvent system works by reducing the interfacial tension between the predominantly aqueous solutions and the hydrophobic solute. Examples of commonly used cosolvents
Ethanol, sorbitol, glycerin, propylene glycol and several members of the polyethylene glycol polymer (PEG200) series are the limited number of cosolvents (of water) those are used and are acceptable in oral preparation. Use of cosolvents Cosolvents are used to increase the solubility of weak electrolytes, non-polar molecules and volatile constituents used to impart a desirable flavor and odour to the product.
DIELECTRIC CONSTANT One property of a solvent system is its dielectric constant. The dielectric constant of a solvent can be defined as the ratio of the capacitances of a capacitor filled with the solvent and air respectively.
Dielectric constant (e ) = C solvent /C air
where, C is the capacitance of the condenser filled
with respective medium (solvent or air)
e.g dielectric water is 78.5
Every solute shows a maximum solubility in any given solvent system, at one or more specific dielectric constants.
To determine the relationship between solubility of a solute with dielectric constant(s) at which maximum solubility is attained is noted.
Pharmaceutical formulations of comparable dielectric constant can thus be prepared, and the most appropriate solvent system can be selected on the basis of solubility, stability and organoleptic characteristics requirements.
SOLUBILIZATION spontaneous increase of solubility of a poorly water-soluble solute molecules into an aqueous solution of surface active agents (or surfactants) in which a thermodynamically stable solution is formed. Mechanism When surfactants are added to water at low concentrations, they tend to orient at the air-liquid interface.
As additional surfactant is added, the interface becomes fully occupied, and the excess molecules are faced into the bulk of the liquid.
At still higher concentrations, the molecules of surfactant in the bulk of the liquid begin to form oriented aggregates or micelles, this change in orientation occurs abruptly (suddenly). The concentration of surface active agent at which micelles occurs is called critical micelle concentration . Solubilization is thought to occur by virtue of the solute dissolving in or being adsorbed onto the micelle. The water solubility of the solute increases with the concentration of the micelles. Examples of some solubilizing agents: .POLYOXYETHYLENE SORBITAN FATTY ACID EASTER (TWEEN SERIES) .POLYOXYETHYLENE MONOALKYL ETHER (BRIJ,MYRJ SERIES ) Other examples are Sucrose monoesters, Lanolin esters etc.
It has generally been found that surface-active-agents having HLB (Hydrophilic Lipophilic Balance) values higher than 15 acts better as solubilizing agents.
COMPLEXATION
Solubility of a compound may be increased by complexing with a complexing agent. e.g. solubility of para amino benzoic acid (PABA) may be increased by complexing with caffeine.
When an insoluble compound forms a complex which is more soluble in the solvent – the total solubility is equal to the inherent solubility of the uncomplexed drug plus the concentration of drug-complex in solution.
When a certain amount of drug is mixed in water some amount will get dissolved (A) and some amount will remain undissolved. If a complexing agent is added to it some drug will be complexed and become soluble in water. So the total solubility will be will be increased.
When more complexing agent is added total solubility will increase; at a certain concentration of complexing agent the solution will become saturated with respect to free drug and the complex (B). After this point if still complexing agent is used then remaining drug (undissolved) will form complex and the excess complex will be precipitated (C). When no drug is left for complexation, complexes of higher order may be formed.
e.g. I2 is sparingly soluble in water. To dissolve it KI (potassium iodide) is added which makes a complex KI.I2 (i.e. KI3). After point C it forms KI. 2I2, KI.3I2 etc.
HYDROTROPHY The term hydrotrophy has been used to designate the increase in solubility in water of various substances due to the presence of large amounts of additives. Mechanism of action
Not clear yet. Some workers have speculated that this phenomenon is more closely related to complexation involving a weak interaction between the hydrotrophic agent and the solute.
Another view is that the phenomenon must be due to change in solvent character because of the large amount of additive needed to bring about the increase in solubility. Examples Since a large concentration of hydrotrophic agent is required (in the range of 20 to 50%) to produce a modest increase in solubility, hence its pharmaceutical applications are very less in number.
Drug —————————Hydrotrophic agent
1. Benzoic acid ———–Sodium benzoate
2. Theophylline ————-Sodium acetate and sodium glycinate
3. Iodine —————Polyvinyl pyrrolidone (PVP)
4. Adrenochrome mono semicarbazone ———-Sodium salicylate
SOLVENTS FOR ORAL PREPARATIONS The solvents those are usually used in the oral liquid preparations are purified water, alcohol, glycerin and propylene glycol.
PURIFIED WATER (H2O) Naturally occurring water exerts its solvent effect on most substances. In oral preparations the water used is potable water or Purified Water USP. Specifications of Purified Water USP Method of preparations : By distillation or by ion-exchange.
Total solid : Less than 10 parts per million (ppm)
pH : Between 5 and 7.
ALCOHOL (ETHANOL) Next to water, alcohol is the most useful solvent in pharmacy.
· It is used as a primary solvent for many organic compounds.
· With water it acts as a cosolvent and increases the solubility of drugs. Alcohol is often preferred because of its miscibility with water and its ability to dissolve many water-insoluble ingredients, including drug substances, flavorants, and antimicrobial preservatives.
· Alcohol is frequently used with other solvents, as glycols and glycerin, to reduce the amount of alcohol required.
· It also is used in liquid products as an antimicrobial preservative alone or as a co-preservative with parabens, benzoates, sorbates and other agents.
Disadvantages It produces pharmacologic and potential toxic effects of alcohol when ingested in pharmaceutical products particularly by children. Hence, it should not be given to children below 6 years. For OTC (over the counter) oral product for children the recommended alcohol-content limit is 0.5 %.
Age of the patient ———–Permitted alcohol content
For children below 6 years ———0.5 %
For children between 6-12 years —–5.0 %
Children over 12 years and adults —–10.0%
GLYCERIN (Glycerol) · Glycerin is a clear syrupy liquid with a sweet taste.
· It is miscible both with water an alcohol.
· Glycerin has preservative qualities. Disadvantages As a solvent, it is comparable to alcohol, but because of its viscosity, solutes are slowly soluble in it unless it is rendered less viscous by heating.
PROPYLENE GLYCOL
It is a viscous liquid, is miscible with water and alcohol. It is useful solvent with a wide range of application and is frequently substituted for glycerin in pharmaceutical formulation.
BUFFERS
A buffer is a compound or mixture of compounds that, by its presence in solution, resists changes in pH upon addition of small quantities of acid or base.
Buffering agents are necessary to resist the change of pH upon dilution or addition of acid or alkali in the liquid preparation.
The usual buffering agents used in oral liquid preparations are acetate buffer and phosphate buffer. Buffer ———Mixture of ———-Buffering Range Acetate buffer ——–Glacial acetic acid
Potassium, sodium, ammonium salt of acetic acid———pH 2.8 to 6.0
Phosphate buffer —-Potassium dihydrogen phosphate
Di-sodium hydrogen phosphate ——pH 2.8 to 6.0
Buffering is required to: 1. Keeping weakly acidic or basic drug in solution
2. Increase the stability of the drug
3. Resist the change of pH upon dilution or addition of acid or alkali (e.g. leaching or alkali from glass container).
SWEETENERS Solutions come in immediate contact with the taste buds (on the tongue). Drugs and other adjuvants are generally not good to taste (i.e. not palatable). To enhance palatability and to mask the taste of the drugs etc. sweeteners are used. Example: Sucrose (sugar), saccharin, aspartame, liquid glucose.
Sucrose
Source Commercially sucrose is obtained from sugarcane, beet root and shorgum. Advantages 1. It is soluble in aqueous medium.
2. It is available in highly purified form at reasonable price.
3. It is chemically and physically stable in the pH range of 4.0 to 8.0.
4. It is frequently used in conjunction with sorbitol, glycerin and other polyols.
5. Above 66.7 % mold growth will not take place. Disadvantages Concentration of sucrose solution above 66.7% (w/w) the sucrose crystallize making the solution hazy (i.e. reducing the gloss of the solution).
Caps of the containers are generally found to be locked due to this crystallization. Sorbitol, glycerin or other polyols are used to reduce the crystallization.
Liquid Glucose Liquid glucose is an extremely viscid substance that imparts both body (i.e highly viscous) and sweetness to liquid formulations. Preparation Partial hydrolysis of starch with strong acid produce liquid glucose. Its main component is dextrose and maltose.
Saccharin (Sodium and Calcium salts are soluble)
Advantages 1. Saccharin is used to supplement sugars and polyols as sweeteners.
2. It is approximately 250 to 500 times as sweet as sugar.
3. It has no calorie value, hence can be given to obese patients and diabetic patients. Disadvantages It has a bitter after taste. Aspartame Aspartame is the methyl ester of aspartic acid and phenylalanine. Advantages 1. It is approximately 200 times sweeter than sugar.
2. No bitter after taste.
3. Solubility in water is adequate for formulation purpose. Disadvantage Although it is very stable as dry powder, its stability in aqueous solutions is pH and temperature dependent. it is stable at pH between 3.4 and 5.0 and at refrigerated temperature.
COLORANTS To enhance the appeal of the vehicle, a coloring agent is generally used which matches well with the flavour employed in the preparation e.g. green with mint, brown with chocolate flavor etc. The colorant used is generally water soluble, non-reactive with other components, and color-stable at the pH range and under the intensity of light that the liquid preparation is likely to be exposed during its shelf-life. N.B. From the psychological point of view the scheme may be as follows: Color—-> Red —–Orange—— Yellow —–Green —–Blue ——Violet
Psychological reactions—–> Exciting —–Cheerful —–Tranquilizing —–Subduing
Desirable properties of a coloring agent 1. Must be harmless, should have no physiological activity
2. It should be a definite compound because then its coloring power will be reliable, its assay practicable.
3. Its tinctorial (coloring ) power should be high so that only small quantities are required.
4. It should be unaffected by light, temperature, micro-organisms, pH changes.
5. It should not interfere with other adjuvants.
6. I must be free from objectionable odour and taste.
7. it must by inexpensive. Example · Coal tar colors e.g. Amaranth
· The permitted colors do not always give satisfactory shades when used alone but most popular tints and shades can be obtained by blending
e.g. Green S and Tartrazine Solution B.P.C. contains GreenS (greenish blue) and Tartrazine (Yellow green)
PRESERVATION Specific organisms generally recognized as undesirable in oral liquids include Salmonella species, Escherichia coli, Enterobacter species, Pseudomonas species (commonly Pseudomonas aeruginosa), Clostridium and Candida albicans.
Source of contamination:
Raw materials, processing containers and equipment, the manufacturing environment, operators, packaging materials and the user.
Characteristics of an ideal preservative 1. It must be effective against a broad spectrum of microorganisms.
2. It must be physically, chemically and microbiologically stable for the life-time of the product.
3. It must be nontoxic, non-sensitizing, adequately soluble, compatible with other formulation components, and acceptable with respect to taste and odour at the concentrations used. Some pharmaceutically useful preservative
Class ——-Preservative ——Usual concentration (%)
Acidic Phenol ————————————–0.2 – 0.5
Chlorocresol ——————————-0.05 – 0.1
o-Phenyl phenol ———————-0.005 – 0.01
Alkyl esters of parahydroxy benzoic acid ——-0.001 – 0.2
(e.g. Methyl and Propyl Paraben)
Benzoic acid and its salts ——————0.1 – .0.3
Boric acid and its salts ——————0.5 – 1.0
Sorbic acid and its salts ———–0.05 – 0.2
Preservatives —————Uses Acidic
Phenol ——————Have characteristic odor and unstable when exposed to oxygen, hence used rarely. Alkyl esters of parahydroxy benzoic acid (e.g. Methyl and Propyl Paraben)————Mostly used
Adequately soluble in water
Have both antifungal and antibacterial activity
Methyl & Propyl ester at a ratio of 10 to 1 produce a synergistic effect. Sodium salt of benzoic acid————–Mostly used Sodium salt of sorbic acid ————-Have antibacterial action and antifungal action
Water soluble Neutral
Chlorbutanol —————–The are volatile alcohols, hence, have odor and loss of preservative action on aging.- Benzyl alcohol
b-phenyl ethyl alcohol———– Not used in oral liquid preparations.Used in ophthalmic, nasal and parenteral products Mercurials ——————Not used in oral liquid preparations
Used in ophthalmic, nasal and parenteral products.
Disadvantage: Mercurials readily reduced to free mercury.
Quartenary ammonium compounds ———-Not used in oral preparations
Used in ophthalmic, nasal and parenteral solutions.Disadvantages: They are inactivated by variety of anionic substances.
SYRUPS Syrups containing approximately 85% sucrose resist bacterial growth by virtue of their exosmotic effect on micro-organisms. Syrups that contain less than 85% sucrose, a sufficient concentration of polyol (e.g. sorbitol, glycerin, propylene glycol or polyethylene glycol) should be added to have the required osmotic pressure.
It is possible, however, for surface dilution to take place in a closed container as a result of solvent evaporation followed by condensation, with the condensate flowing back onto the liquid surface. The resulting diluted medium for bacterial and fungal growth. A sufficient concentration of preservative or 5 to 10% ethanol should be added to arrest the growth of microorganisms.
FLAVORS An objectionable taste may lead to nausea, vomiting and refusal to take the preparation regularly or at all. On the other hand, an attractive flavour will encourage continuation of treatment.
The four basic taste sensations are salty, bitter, sweet and sour. A combination of flavoring agents is usually required to mask these taste sensations effectively. Flavor selection Taste sensation ———–Recommended flavor Salty —————-Butterscotch, maple, apricot, peach, vanilla, wintergreen mint.
Bitter ————–Wild cherry, walnut, chocolate, mint combinations, anise etc.
Flavor adjuncts
Menthol, chloroform and various salts frequently are used as flavor adjuncts.
Menthol and chloroform are sometimes referred to as desensitizing agents. They impart a flavor and odor of their own to the product and have a mild anaesthetic effect on the sensory receptor organs associated with taste.
MANUFACTURING CONSIDERATION
Raw materials
1. Incoming raw materials should be tested against some specifications regarding identity, purity, uniformity and freedom from excessive microbial contamination.
2. Additional processing may be required e.g. size-reduction or sterilization before manufacturing. It is usually much easier to begin with low microbial counts in the raw materials than to try to reduce these counts substantially during processing.
3. In oral liquid preparations water is the main vehicle. It should meet the USP requirements for Purified water. It may be obtained by distillation or ion-exchange treatment. To reduce the microbial burden water is passed through UV-rays and constant circulation in piping systems that have “dead ends” where micro-organisms can thrive.
EQUIPMENTS The following types of equipments may be used in the manufacture of oral liquid solutions:-
1. Mixing tanks (SS 316 Stainless Steel) equipped with an agitator.
2. Measuring devices for large and small amount of solids and liquids.
3. A filtration system for the final polishing – e.g. Sparkler filter.
Cleaning of equipments All equipments must be thoroughly cleaned and sanitized before use.
Disinfectants used: Dilute solutions of H2O2, phenol derivatives and paracetic acid.
Sterilized by: Alcohol, boiling water, autoclaving, steam or dry heat.
Material of construction
· Tanks are usually constructed of polished stainless steel and are usually jacketed to allow for heating or cooling of the contents.
· Tanks are covered and equipped with see-through charging ports and illumination for easy observation of the contents. If the tanks are used for compounding of the bulk liquid, they have a built in agitation system.
· The compounded liquid may then be transported to the filling line, either manually by filling into portable transport tanks (fitted with wheels) or by pumping (or gravity flow) through a liquid delivery conduit.
· All the equipments and pipe lines should be easy to disassemble, clean and sanitise.
COMPOUNDING PROCEDURE Objective Complete solution should usually be confirmed at every stage in the manufacture of a homogeneous liquid. Formula 1. Active constituent / Drug
2. Vehicle (Water / Alcohol / Glycerol)
Sweetening agents (viscosity building agents) Syrup, Sorbitol, Glycerol
3. Preservatives
4. Flavors
5. Colors (Dyes) Steps of preparation
1. Purified water is heated to approximately 500C to facilitate the dissolution of the solid solutes. Solid solutes are added to the warm water and stirred to dissolve (e.g. sugar, drug).
2. If any additive is required in small amount then it should be dissolved separately and then mixed with the bulk mixture.
3. Any large volume liquids (e.g. glycerol, sorbitol solution) are added and mixed until homogeneous.
4. Before adding flavors the temperature should be reduced to 300C (since most of the flavors are volatile). The flavor should be dissolved in small amount of alcohol (since flavors are generally insoluble in aqueous medium) and then it is mixed with the bulk mixture.
5. Dye should be dissolved n small amount of water. Then transferred to the bulk mixture.
6. Finally volume is made up to the required volume. The total mixture is agitated thoroughly until homogeneity is obtained.
7. Finally the batch is filtered to obtain a polished, clear solution.
ORAL SOLUTIONS
Liquid system where all the solutes remain in dissolved state is known as solution. Solutions intended to be taken orally is called oral solutions.
Advantages 1. Absorption is instant from the gastro-intestinal tract.
2. Uniform dosage is certain.
3. They provide a safe means of administering substances like potassium iodide that cause gastric pain if taken dry, e.g. as powders or tablets.
4. The attractive appearance of a solution in a well polished bottle has a beneficial psychological effect.
Dose Liquid pharmaceuticals for oral administration are usually formulated such that the patient receives the usual dose of the medication in a conveniently administered volume, as 5 ml (one teaspoonful), 10 ml or 15 ml (one table-spoonful).
On the other hand many solutions used in paediatric patients are given by drop, utilizing a calibrated dropper usually furnished by the manufacturer in the product package.
Calculation The strengths of pharmaceutical preparations are usually expressed in terms of % strength (w/w, w/v, v/v).
Formulation Some chemical agents may be slowly soluble. In this case rate of dissolution may be enhanced by
1. application of heat: the temperature should not destroy other ingredients.
2. decrease the particle size to increase the specific surface area.
3. by agitation: but dissolution is delayed compared to heat application.
Chemical interaction
Chemical interactions which may occur between the various components of a solution which may result in a alteration in the preparation’s stability and / or potency. For example, it has been demonstrated that esters of p-hydroxy benzoic acid (methyl-, ethyl-, propyl- and butyl- parabens) frequently used preservatives in oral preparations, have a tendency to partition into certain flavoring oils.
SYRUPS · Syrups are concentrated, aqueous preparations of a sugar or sugar-substitute with or without added flavoring agents and medicinal substances.
· Syrups containing flavoring agents but not medicinal substances are called flavored vehicles (syrups).e..g Cherry Syrup, Cocoa Syrup, Orange syrup, Raspberry Syrup.
· Syrups containing medicinal agents are called medicated syrups. e.g. Chlorpheniramine maleate syrup, Ipecac syrup, Chloral hydrate syrup etc.
Components of syrups Most syrups contain the following components in addition to the purified water and any medicinal agents present:
1. the sugar, usually sucrose, or sugar substitutes used to provide sweetness and viscosity,
2. antimicrobial preservatives,
3. flavorants, and
4. colorants.
Sucrose and non-sucrose based syrup Sucrose is most frequently employed in syrups. In special circumstances it may be replaced by sugars, such as, dextrose, or non-sugars as sorbitol, glycerin and propylene glycol.
Methyl cellulose or hydroxyethyl cellulose -these two materials are not hydrolyzed and absorbed into the blood stream, and their use results in an excellent syrup-like vehicle.
Taste masking by syrup
The syrup imparts a characteristics “body” (viscosity) and together with the sweetness and the flavorants results in a type of pharmaceutical preparation that is quite effective in making the taste of added medicinal agents. When the syrup is swallowed, only a portion of dissolved drug actually makes contact with the taste buds, the remainder of the drug being carried past them and down the throat in the containment of the viscous syrup.
In the case of antitussive syrups (e.g. linctus) the thick sweet syrup has a soothing effect on the irritated tissues of the throat as it passes over them.
Preservative action of syrup
Simple syrup NF contains 85% w/v sucrose. At this concentration the syrup is resistant to microbial growth, due to unavailability of the water required for the growth of micro-organisms.
85% w/v syrup has a specific gravity of 1.313
i.e. 100 ml syrup contains 85 gm sucrose
Weight of 100 ml syrup = 100 x 1.313 = 131.3 gm
Weight of water present in 100 ml syrup = (131.3 – 85) gm
= 46.3 gm
Volume of water present in 100 ml syrup =46.3 ml
Volume of sucrose present in 100 ml syrup = (100 – 46.3) ml
= 53.7 ml
100 ml 85% syrup contains
NAME—–Weight————-Volume
Sugar ——-85.0 g——-53.7 ml
Water ——46.3 g——-46.3 ml
Syrup (total) —–131.3 g ——100.0 ml
The solubility of sucrose in water is 1 g in 0.5 ml
to dissolve 85 g sugar required will be = 85 x 0.5 ml
= 42.5 ml
Thus, only a very slight excess of water (46.3 – 42.5 = 3.8 ml per 100 ml of syrup) is employed in the preparation of syrup. The sight excess of water permits the syrup to remain physically stable under conditions of varying temperature.
If the syrup were completely saturated with sucrose, under cool storage conditions some sucrose might crystallize from solution and, by acting as nuclei, initiate a type of chain reaction that would result in the separation of an amount of sucrose disproportionate to its solubility at the storage temperature. The syrup would then be very much unsaturated and probably suitable for microbial growth. However, the syrup NF is stable and resistant to crystallization as well as to microbial growth.
Preparation of Syrups
Syrups are frequently prepared by one of four general methods; depending upon the physical and chemical characteristics of the ingredients.
1. Solution of the ingredients with the aid of heat
2. Solution of the ingredients by agitation without the use of heat
3. Addition of sucrose to a prepared medicated liquid or to a flavored liquid and
4. by percolation of either the source of the medicating substance or of the sucrose.
Solution with the aid of heat The sugar is generally added to the purified water, and heat is applied until solution is effected. Then other required heat-stable components are added to the hot syrup, the mixture is allowed to cool, and its volume is adjusted to the proper level by the addition of Purified Water.
The use of heat facilitates the rapid solution of the sugar as well as certain other components of syrups.
If excessive heating occurs then sucrose may be hydrolyzed into dextrose (D-glucose), and fructose (levulose). This hydrolytic reaction is referred to as inversion, and the combination of the two monosaccharides is invert sugar. When heat is applied in the preparation of a sucrose syrup, some inversion of the sucrose is almost certain. The speed of inversion is greatly increased by the presence of acids, the hydrogen ion acting as a catalyst to reaction.
Invert sugar is more sweeter than sucrose, and normally colorless. Syrup darkens due to the effect of heat on the fructose. When the syrup is greatly overheated, it becomes amber colored due to the caramelization of the sucrose. Syrups so decomposed are more susceptible to fermentation and microbial growth.
Because of the prospect of decomposition by heat, syrups cannot be sterilized by autoclaving. Solution by agitation without heat Sucrose and other formulation agents may be dissolved in purified water by placing the ingredients in a vessel of greater capacity than the volume of syrup to be prepared, thus permitting the thorough agitation of the mixture.
Addition of sucrose to a medicated liquid or to a flavored liquid Medicated liquid such as tincture or fluid extract is employed as the active ingredient in the preparation of syrup.
If the extract contains alcohol soluble ingredients and the alcohol amount is high then sucrose is added directly and stirred.
If alcohol content is low and all the ingredients are water soluble then the liquid extract is directly mixed with a prepared syrup. Preparation of syrup by percolation
In this method purified water or an aqueous solutionis passed slowly through a bed of crystalline sucrose, thus dissolving it and forming the syrup. If required a poriton of the percolate is recycled.
Preparation of a multivitamin syrup Formula: Each 15 ml contains Active ingredients
Vitamin B1 4.5 mg
Vitamin B2 2.5 mg
Vitamin B6 1.5 mg
Niacinamide 30 mg
D-Pantothenol 5 mg
Taste enhancer
Citric acid 0.008% (w/v)
Flavours q.s. Colours
Caramel q.s. Vehicle
Purified water 15 ml Procedure 1. Primary Syrup is prepared as usual, filtered and cooled to room temperature. The material is transferred to the mixing tank and stirring is started.
2. Vitamin B1 is dissolved in small volume of water and added to the syrup.
3. Vitamin B2 is slightly soluble in water, hence, it is dissolved with the aid of 10% sodium hydroxide. Vitamin B6 is also added to dissolve. The mixture is transferred to the mixing tank.
4. Niacinamide is dissolved in small amount of water and added to the mixing tank.
5. D-pantothenol is dissolved in hot water, cooled and transferred to the syrup.
6. Sorbitol and glycerin are added.
7. All the preservatives are dissolved in small volume of water and added to the syrup.
8. Citric acid and disodium edetate is dissolved separately in water and then mixed to the syrup.
9. Flavors and color are added and the final volume is made up with water.
10. Mixed for 2 hours and filtered.
Expected Questions 1. Short note on preservatives in pharmaceutical dosage forms. (98)
2. Short note on syrups. (98)
3. Give the importance of colorants, sweeteners, solvents, stabilizers, flavoring agents in pharmaceutical dosage forms. (98)
4. Discuss the preformulatory and informulatory aspect of designing a multivitamin syrup.
5. What are syrups? Write about the preparation, properties and uses of at least two medicated syrups. (93)
6. Differentiate between solution and elixirs. (95)
7. Classify organoleptic compounds with examples. (93)
1. Kinetics and Reaction Mechanism. Kinetic and thermodynamic
product control, principle of microscopic reversibility, isotope effect on
kinetic effect of reaction medium on the rate of the reaction
5
2. Transition state theory. General theory of the transaction state, the
reaction coordinate, rate determining transition state, Curtin principle.
4
3. AcidBase Catalysis. General mechanisms of acid and base
catalyzed reactions, rates of acid and base catalyzed reactions, Bronsted catalysis correlation of reaction rates with acidity functions.
5
4. ChargeTransfer complexes and reactions. Definition of Complex, Charge transfer transition, donors and acceptors, ground state
charge transfer contribution.
5
5 Coordination Chemistry, Nomenclature, Theories of bonding in co ordinate complexes, Stability of complexes and chelation. 5
6.
Brief introduction to the inorganic medicinal compounds:
antacid(Magnesium trisilicate and aluminium hydroxide ), antimicrobial (hydrogen peroxide and povidoneiodine),
astringent(Zinc oxide) and Pharmaceutical aid(tale and barium
sulphate)
6
Reference Books:
1. Isrie V. Anslyn and Dennis A. Dougherty, Modern Physical Organic Chemistry, John
Wiley, 2006
2. Neil Isaacs, Physical Organic Chemistry, 2 nd Edition, Pearson Education 1995
3. Louis P. Hanunett, Physical Organic Chemistry, Megraw Hill Education, 2 nd Rev
Edition, 1970
4. Edward M. Kosower, An Introduction to Physical Organic Chemistry, John Wiley and
Sons, Inc, 1968
5. J.D Lee, A New Concise Inorganic Chemistry, 3 rd edition Van Nostrand Reinhold
Company Ltd.
6. John H. and Edward B., Inorganic Medicinal and Pharmaceutical Chemistry Varghese
Publishing House, 1986.
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ORGANIC CHEMISTRY –I 3hrs/ week
S. No. Topic Hours
1.
Structure and Properties of Organic Compounds : Types of bonds in
organic compounds, hybridization of orbital’s, formation of the same
and bonds formed, bond length, bond angles, bond energles, bond
polarization
4
2.
Inductive effects, concepts of Hbonding hyperconjugation resonance, Van der Waal’s interaction, inclusion phenomena, Acidity and basicity
of molecules
4
3. Concept of Electrophiles and Nucleophiles
Calculations for determining empirical and molecular formulae
3
4.
Mechanism and elementary stereochemistry discussion of SN1, SN2
and Sn1 mechanisms, En, E2 and E Discussion of substitution vs. elimination
7
5.
Discussion of the following classes of compounds in brief, with regard
to IUPAC nomenclature, sources, methods of preparation, Physical
properties and general reactions of hydrocarbons (alkanes, alkenes, alkynes)
5
6.
Addition reaction of alkenes: Markonikov, AntiMarkonikov rules, Hydroboration, OxymercurationDemercuration, Ozonolysis, addition
of KMnO4 and Addition reactions across conjugated.
6
7. Aliphatic halogen compounds 2
Reference Books:
1. Robert T. Morrison and Robert N. Boyd, Organic Chemistry, 6 th Edition, Pearson
Education Pvt. Ltd., 2005
2. Peter Sykes, A Guide book to Mechanisms in organic Chemistry, 6 th Edition, Pearson
Education, 2007
3. H. Finar, Organic Chemistry, 5 th Edition, Pearson Education, 2006
4. Stanley Pine, Organic Chemistry, 5 th Edition, McGraw Hill Companies, 2007
5. Francis Carrey, Organic Chemistry, 4 th Edition, McGraw Hill Companies,2000
ANATOMY, PHYSIOLOGY AND PATHOPHYSIOLOGY I 3hrs/ week
S. No. Topic Hours
1. Brief Introduction to human body and organization of human body 1
2.
Structural and functional characteristics of following tissues
· Epithelial
· Connective
· Nervous
· Muscle
2
3. Detailed structure of cell membrane and transmembrane movement of
substances
2
7 | P a g e
4.
Components and functions of lymphatic system:
· Lymphatic organs and tissues
· Organization of Lymph vessels
· Formation and flow of lymph
2
5.
Definition and etiology of following diseases in detail
· AIDS
· Autoimmune disease (Rheumatoid arthritis /Grave’s disease /
Myasthenia Gravis / Rheumatic fever)
· Hypersensitivity (Allergy)
3
6.
Haematology
· Composition of blood
· Functions of blood elements
· Erythropoiesis
· Synthesis of Haemoglobin
· Leucopoisis
· Coagulation of blood
· Blood groups
8
7.
Definition & etiology of following diseases , in detail
· Anaemias Types of anaemias
· Polyeythemia
· Leucopenia
· Leukocytosis
· Thrombocytopenia
· Leukemia
4
8.
Structure and Properties of following muscles
· Cardiac muscles
· Smooth muscles
· Skeletal muscles
· Neuromuscular transmission and contraction of skeletal muscle
· Energy metabolism in the muscle
· Types of muscle contractions
· Muscle tone
7
9.
Definition and etiology of following diseases, in detail
· Spasticity
· Tetany
1
Reference Books:
1. Anne Waugh and Alleon Grant Ross & Wilson’s Anatomy & Physiology in Health & 9 th
Edition (2001) Churchill Livingstone, Edinbrigh, London, Newyork.
2. Gerald J. Tortora & Sandra Reynolds Grabowaski Principle of Anatomy & Physiology
10 th Edition (2003) John Wiley & Sons Inc, Newyork, USA
3. Arthur C. Guyton & John Half. Textbook of Medical Physiology 10 th Edition (2000)
W.B. Saunders Company, Philadelph , Pensylvania, USA
4. B. R. Mackenna & R. Callander Illustrated Physiology 6 th Edition 1997, Churchill
Livingstone, Newyork Edinburgh, London
5. Praful b. Godkar Textbook of Medical Laboratory Technology 2 nd Edition 2006
Bhalani Publishing House, Mumbai
6. V. G. Ranade, P. N. Joshi & Shalini Pradhan A Text book of Practical Physiology 3 rd
Edition 1982 P.V.G. Prakashan, Pune 30
8 | P a g e
PHYSICAL PHARMACY I (3hrs/ week)
S. No. Topic Hours
1. Gases:
· Ideal and Real Gases
· Vanderwaals phenomenon
· Critical phenomenon, critical constants and their determination
· Liquefaction of gases – Linde’s process and Claude’s process
· Application of Liquefaction in aerosols introduction to the
concept
6
2. Physical Properties of Drug Molecules
· Additive, constructive and colligative properties with examples
· Dipole moment, significance to pharmacy, concept of
polarisability and molar
· Polarisation
· Retractive index and molar refraction and application of moral
retraction to determine structures. · Viscosity: Definition, Concepts and applications > Textbook of
Pharmacy Subramanyam
· Optical rotation and specific rotation and its application
6
3. Solutions of Nonelectrolytes:
· Units for expressing concentration
· Ideal and real solutions
· Raoults law, deviation from Raoults law
· Methods to measure vapour pressure lowering and its
application (problems)
· Distillation of binary mixtures and azeotropic distillation
· Concept of steam distillation
· Elevation of boiling point and determination of molecular weight
(problems)
· Depression of freezing point and determination of molecular
weight (Problems)
· Osmotic pressure: Concept, Methods to determine, molecular
weight determination from osmotic pressure
9
4. Thermodynamics
· Definition, Application and Limitations
· Systems –Homogenous, Heterogenous
· Types of systems Open, Closed, Adrabatic, Isothermal
· Types of Properties Intensive and Extensive Property
· Equilibrium and NonEquilibrium states
· Types of Processes Isothermal Adrabatic, Isobanic, Isochoric, Cyclic Process
· Reversible and Irreversible process
· First Law of thermodynamics
· Enthalpy, heat Capacity, cP cVR (Derivation)
· Work of expansion against variable pressure
Thermochemistry
· Heat of reaction, Heat of Formation, Heat of combustion, Heat of
Solution – Differential and Integral heat of solution.
· Bond Energy – Calculation of Heat of reaction from bond energy
9
9 | P a g e
data
· Kirehoffs equation, Hess’s law of constant heat summation
· Second law of thermodynamics
· Carrot theorem
· Efficiency of heat engine
· Entropy
· Third law of thermodynamics
Free Energy and its applications
· Pressure and Temperature coefficients of free energy
· Maximum net work, Criteria for equilibrium
· Chemical potential (only definition)
· Gibbs Helmholtz equation
· Clausius Clapereyon equation No derivation
· Vant Holf equation No derivation
5. Properties of Solutions of Electrolytes
· Electrolysis
· Faradays laws of electrolysis
· Electrolytic conductance, Specific conductance, Equivalent
conductance, Molecular conductance
· Transport Number
· Measurement of conductance
· Variation of equivalent conductance with
· Arrhenius theory of electrolytic dissociationcolligative properties, activity coefficient expressing collagative properties. · Theory of strong electrolytes
· Degree of dissociation
· Kohlrauschs law of independent migration of
· Application of conductivity measurements conductometric
titrations and solubility of a sparingly soluble salt
· Equivalent conductance of a weak electrolyte at infinite dilution
· Degree of dissociation of a weak electrolyte
9
Reference Books:
1. P. J. Sinko, “Martin’s Physical Pharmacy and Pharmaceutical Science” 5 th Edition, Lippincotts Willians and Wilkin, Indian Education Distributed by B. I. Publications
Pvt. Ltd, 2006. 2. A. Findlay, “Practical Physical Pharmacy’ revised and edited by J. A. Ktchener, 8 th
Edition. Lonmans, Green and Company Ltd 1967. 3. B. S. Bahl, A. Bahl, G. D. Tuli, “Essentials of Physical Chemistry” revised edition,
S. Chand and company Ltd, New Delhi, 2006. 4. U. B. Hadkar “A Textbook of Physical Pharmacy”, 6th Edition Nirali Prakashan,
Pune 2006. 5. U. B. Hadkar, T. N. Vasudevan, K. S. Laddha “Practical Physical Pharmacy” Yucca
Publishing House, Dombivali, 1994.
PHARMACEUTICSI 3hrs/week
S. No. Topic Hours
10 | P a g e
1. Historical background to the profession of Pharmacy in India in brief. Brief overview of status of Pharmaceutical industry in India
2
2.
Introduction to Pharmacopoeias. Development of Indian Pharmacopoeia and other Compendia
including B.P.,U.S.P., N.F., Ph Eur., International pharmacopoeia and
B.P.C.
3
3. Definition of Drug
Concept of dosage form and formulation – Scope of Pharmaceutics
Routes of administration and physiological considerations
Classification of dosage forms and their applications.
3
4.
Drug administration: Introduction to bioavailability and
biopharmaceutics. Concepts of drug efficiency and dose response.
Introduction to Absorption, Distribution and fate of drug.
4
5. Pharmaceutical Calculations: Reduction and enlargement of formula,
Formula by weight (w/v, w/w, v /v); in parts. 3
6. Introduction to Good Manufacturing Practices and Quality Assurance 2
7.
Introduction to galenicals. A method of preparation of extracts includes
maceration, percolation, decoction, infusion and digestion. 3
8.
Introduction to alternate systems of medicine: Ayurveda, Homeopathy, Unnani and Siddha. 1
9. Delivery systems: Non – sterile monophasic liquids. Unit operation of : Filtration and clarification ( Theory and equipment
for filtration of solid from liquids ) and mixing
8
10. Rheology : Definition and concepts, types of flow, thixotropy and
measurement of flow properties
3
Total 33
Reference Books:
1. L. V. Allen Jr., N. G. Popovich and H. C. Ansel “Ansel’s Pharmaceutical Dosage
Forms and Drug Delivery Systems “,8 th Edition Lippincotts Williams and Wilkin, Indian
Education Distributed by B. I. Publications Pvt. Ltd, 2005
2. P. J. Sinko, “Martin’s Physical Pharmacy and Pharmaceutical Science” 5 th Edition, Lippincotts Williams and Wilkin, Indian Edn, Distributed by B. I. Publications Pvt. Ltd,2006
3. M. E. Aulton “Pharmaceutics The Science of Dosage Form Design” Churchill
Livingstone, London, 2002. 4. “Remington The Science and Practice of Pharmacy “, Vol. I and II, 21 st Edn. Lippincotts Williams and Wilkin, Indian Edn. Distributed by B. I. Publications Pvt. Ltd.,2005
5. M. L Shroff “Principles of Pharmacy Part I and II”8 th Edn. Five star Enterprises, Calcutta. 6. E. A. Rowling “Bentleys Textbook of Pharmaceutics” 8 th Edn. Bailliere Tindall, London, Indian Edn. Published by All India Traveler Book Seller Delhi, 1992.
11 | P a g e
7. P. C. Dandiya, R. K. Khat and N. K. Gurbani “The Pharmacist Year Book 1993
1 st Edn. CBS Publishers and Distributors, Delhi 1993. 8. G. Sonnedecker “Kremers and Urdang’s History of Pharmacy” 4 th Edn Lippincotts
Company, USA, 1976.
9. R. A. Lyman and G. Urdang “American Pharmacy” 5 th Edn.
10. James Swarbick “Current concepts in Pharmaceutical Sciences: Dosage form
design and bioavailability” Lea and Febiger, Philadelphia, 1973.
11. Harkishan Singh “Pharmacopoeias and Formularies” Vol. I Vallabh Prakashan,
Delhi 1994. 12. S. J. Carter “Cooper and Gunn’s Tutorial Pharmacy” 6 th Edn. CBS Publishers and
Distributors, Delhi, 1986.
13. M. J. Stocklosa, H. C. Ansel,”Pharmaceutical Calculations” 8 th Edition, Indian
Edition by K.M. Varghese Company, Mumbai 1986.
PHARMACEUTICAL ENGINEERING I 3hrs/ week
Note: Only principles and equipments to be covered
No mathematical derivations and numerical problems
S. No. Topic Hours
1. Fluid Flow:
· Mention fluid properties such as Viscosity, compressibility and
surface tension of fluids
· Hydrostatics influencing fluid flow
· Fluid dynamics – Bernoulli’s theorem, flow of fluids in pipes,
laminar and turbulent flow.
4
2. Heat Transfer:
· Modes of heat transfer – conduction, convention and radiation.
· Fourier’s law for slabs and pipes (only equation and factors
affecting)
· Concepts of thermal conductivity and steady state heat transfer. · Compound resistance in series. · Heat transfer by convection – Natural convection and forced
convection, dimensional analysis. Heat transfer between fluid and
solid boundary. · Heat transfer by radiation – Kirchhoff’s law and Stefan Boltzmann
law. (only equation and factors affecting)
· Overall heat transfer coefficient
· Heat exchangers tubular and plate
6
3. Mass transfer:
· Mass transfer in turbulent and laminar flow
· Concept of interfacial mass transfer.
2
4. Pumping:
· Positive displacement pumps reciprocating pumps, rotary pumps
· Centrifugal pumps
· Special pumps
4
5. Measurements:
· Measurement of flow – Classification of flow meters, venture
4
12 | P a g e
meter, orifice meter, pitot tube, rotameter and current flow meters
· Pressure measurement – Classification of manometers, simple
manometer, U tube manometer and modifications, Bourdon gauge
6. Conveying of Solids:
· Belt conveyor, Bucket conveyor, screw conveyor and Pneumatic
conveyor.
1
7. Water Purification:
· Pretreatment and purification by deionization, reverse osmosis and
distillation.
2
8. Refrigeration and Air Conditioning:
· Water vapour air mixture
· Hygrometry
· Humidification and dehumidification equipments – spray ponds, natural draft cooling towers and mechanical draft cooling towers. · Refrigeration equipment and concept of refrigeration load,
concepts of brine systems and absorption systems
4
9. Centrifugation :
· Principle , objective and requirements of centrifugation
· Equipments Hydro extractors.
1
10. Corrosion:
· Mechanism and types of corrosion. · Factors influencing rate of corrosion.
· Methods of combating corrosion.
3
11. Material of Construction:
· Classification into metals & nonmetals
· Ferrous and its alloys – cast iron, mild steel and stainless steel
· Copper and its alloys
· Nickel and its alloys
· Aluminum and its alloys
· Glass
· Plastics – Classification into thermoplastics and thermosetting
plastics Properties and applications of polyvinyl chloride,
polyethylene, polypropylene, polystyrene, polyster, ABS, phenolic
and epoxy plastics, fluorocarbon plastics, chlorinated plastics and
poly carbonate plastics.
4
Total 35
Reference Books:
1. K. Sambamurthy “Pharmaceutical Engineering” New Age International Pvt. Ltd. New
Delhi, 2001.
2. A. R. Paradkar “Introduction to Pharmaceutical Engineering”7 th Edn. Nirali
Prakashan, Pune 2005. 3. W. L. Badger and J. T. Banchero “Introduction to Chemical Engineering” Mc. Graw
Hill Book Company. 4. R. H. Perry and D. W. Green “Perry’s Chemical Engineer’s Handbook “7th Edn.
Chemical Hand Book. Mc Graw Hill Book Company, 1997.
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ORGANIC CHEMISTRY LABORATORY I 4hrs/ week
Organic Sporting: Qualitative analyses of organic compounds – aspects to be covered are
solubility characterization and preliminary tests, elements detection, functional group
characterization, derivative preparation
Reference Books:
1. Textbook of practical organic chemistry by Vogel, 4 th edition, publishers Longman
group Ltd. 2. Practical Organic Chemistry by F.G. Mann and B.C. Saunders, 4 th edition published
by OrientLongman.
3. Handbook by Kulkarni and Pathak, Published by Dastane Ramchandra and Company
PHYSICAL PHARMACY LAB – I 4hrs/ week
1. Determination of refractive index, molar refraction. Using water as a reference
standard to determine refractive index of two organic solvent and their mixtures and
to determine composition of unknown. To determine RI of a solid (KCI) from two
concentrations of solid solutions. 2. Viscosity: To determine the composition of the unknown binary mixture.
3. Polarimetry: Different Concentrations of sugar, determination of unknown
concentration and specific rotation.
4. Determination of molecular weight by Rast camphor method. Demonstration of
Landsberger method.
5. Determination of heat of solution.
6. Partition coefficient – Iodine
Reference Books:
1. U. B. Hadkar, T. N. Vasudevan, K. S. Laddha “Practical Physical Pharmacy” Yucca
Publishing House, Dombivali, 1994.
ANATOMY, PHYSIOLOGY AND PATHOPHYSIOLOGY – Lab (4hrs/ week)
1. Hematology
a. Red Blood Cell (RBC) Count
b. Total Leukocyte Count
c. Differential Leukocyte (WBC) Count
d. Hemoglobin content of blood
e. Bleeding & Clotting Time
f. Blood groups
g. Erythrocyte Sedimentation Rate (ESR)/ Hematocrit (Demonstration)
2. Study of Human Skeleton
3. Microscopic study of permanent slides Tissues:
‐ Columnar, Cuboidal, Squmaous, Ciliated Epithelium
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‐ Cardiac/Skeletal/ Smooth muscle
‐ Ovary,Testis, Liver, Pancreas, Thyroid, Tongue, Stomach, Intestine, Kidney, Lung, Spinal Cord, Cerebrum, Artery, Vein
4. Measurement of blood pressure
5. Tutorial Discussion on some common investigational procedures used in diagnosis
of disease with the help of charts slides Name and Importance of following tests:
1. Electroencephalogram (EEG) in diagnosis of Epilepsy
2. Electrocardiogram (ECG) in diagnosis of cardiac arrhythmia
3. Liver Function Tests
· Serum Bilirubin
· Serum glutamate oxaloacetate transaminase (SGOT)
· Serum glutamate pyruvate transaminase (SGPT)
· Urine Bilirubin
· Urine Urobilinogen
4. Kidney Function Tests
· Serum Creatinine
· Serum Urea, Uric Acid
· Blood Urea Nitrogen(BUN)
5. Blood Glucose
6. Serum Cholesterol/ Triglycerides
7. Serum Alkaline phosphatase (ALT)
8. Serum Acid phosphatase (APT)
9. Serum Lipase
10. Serum Amylase
11. Serum Calcium
12. Serum lactate dehydrogense (LDH)
13. Thyroid Function Tests T3, T4
14. Diagnostic tests for infectious diseases like
· Malaria
· Tuberculosis
· Dengue
· Leptospirosis
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Reference Books:
1. Anne Waugh And Allison Grant Ross & Wilson’s Anatomy & Physiology in Health &
Illness 9 th Edition (2001) Churchill Livingstone, Edinbruigh, London, Newyork.
2. Gerald J. Tortora & Sandra Reynolds Grabowaski Principals of Anatomy &
Physiology 10 th Edition (2003) John Wiley & Sons Inc, Newyork, USA
3. Arthur C. Guyton & John E. Hall Textbook of Medical Physiology 10 th Edition (2000)
W. B. Saunders Company, Philadelphia, Pensylvania, USA. 4. B. R. Mackenna & R. Callander Illustrated Physiology 6 th Edition, Churchill
Livingstone, Newyork Edinburgh, London.
5. Praful B. Godkar Textbook of Medical Laboratory Technology 2 nd Ed. 2006 Bhalani
Publishing House, Mumbai
6. V. G. Ranade, P. N. Joshi & Shalini Pradhan, A Textbook of practicalphysiology,3 rd
Edition 1982 P.V.G. Prakashan, Pune 030.
Mumbai University B.Pharm syllabus
SEMESTER – II Syllabus First year:
ANATOMY, PHYSIOLOGY AND PATHOPHYSIOLOGY –II 3hrs/ week
S. No Topic Hours
1. Anatomy and physiology of Respiratory System
‐ Exchange of gases
‐ External and Internal respiration
‐ Mechanism and regulation of respiration
‐ Lung volumes and lung capacities
4
2. Definition and etiology of following diseases, in detail
‐ Asthma
‐ Pneumonia
‐ Bronchitis
‐ Emphysema
‐ Respiratory Acidosis and Alkosis
3
3. Reproductive System
‐ Anatomical and Physiological considerations of male and
female reproductive system
‐ Menstrual cycle
4
4. Definition and etiology of following diseases, in detail
‐ Infertility
‐ Sexually transmitted diseases (STD)
‐ Dismenorrhea
2
5. Endocrine System
Location hormones and functions of following endocrine glands:
‐ Pituitary
‐ Thyroid & Parathyroid
‐ Adrenal
‐ Pancreas
‐ Tests & Ovaries
‐ Control of hormone secretion
12
6. Etiology of hypo and hyper secretion of above endocrine glands
and related diseases
5
Reference Books
1. Anne Waugh And Allison Grant Ross & Wilson’s Anatomy & Physiology in Health &
Illness 9 th Edition (2001) Churchill Livingstone, Edinbrigh, London , Newyork
2. Gerald J. Tortora & Sandra Reynolds Grabowaski Principals of Anatomy &
Physiology 10 th Edition (2003) John Wiley & Sons Inc, Newyork, USA
3. Arthur C. Guyton & John E. Hall Textbook of Medical Physiology 10 th Edition (2000)
W. B. Saunders Company, Philadelphia, Pensylvania, USA
4. B. R. Mackenna & R. Callander Illustrated Physiology 6 th Edition 1997, Churchill
Livingstone, Newyork Edinburgh, London
5. Praful B. Godkar Textbook of Medical Laboratory Technology 2 nd Edition 2006
Bhalani Publishing House, Mumbai
6. V. G. Ranade, P. N. Joshi & Shalini Pradhan A Textbook of practical physiology, 3 rd
Edition 1982 P. V. G. Prakashan, Pune 30
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ORGANIC CHEMISTRY – II 3hrs/ week
S. No. Topic Hours
Discussion of the following classes of compounds in brief, with regard
to IUPAC nomenclature, sources, methods of preparation, Physical
properties and general reactions, with mechanisms
1. Alcohols and ethers 4
2. Carbonyl compounds (aldehydes and ketones) 5
3. Carboxylic acids, esters, anhydrides, amides 5
4. Amines and other nitrogen containing compounds. 6
5. Aromatic compounds: Concepts of aromaticity and aromatic character, Huckel rule, structure and resonance in benzene; Nomenclature of
aromatics: Electrophilic and nucleophilic sunstitution reactions in
aromatic compounds.
10
6. Preparation and reactivity of polycyclic aromatics – naphthalene’s
anthracene and phenanthrene
6
Reference Books
1. Morrison and Boyd, Organic Chemistry, 6 th Edition, Pearson Education Pvt. Ltd, 2006. 2. Peter Sykes, A Guidebook to Mechanisms in organic Chemistry, 6 th Edition, Pearson
Education, 2007.
3. I. L. Finar, Organic Chemistry, 5 th Edition, Pearson Education, 2006 Stanley Pine,
Organic Chemistry, 5 th Edition, Mc Graw – Hill Companies, 2007. 4. Francis Carrey, Organic Chemistry, 4 th Edition, Mc Graw – Hill Companies, 2000.
PHARMACEUTICAL ANALYSIS – I 3 hrs/ week
S. No. Topic Hours
1. Introduction to the study of monographs of five official compounds – sodium chloride, calcium carbonate. Talc, boric acid and ferrous
sulphate.
4
2. I.P. Limits tests for insoluble matter, soluble matter, nonvolatile
matter, volatile matter, residue on ignition and ash value.
3
3. Various limit tests prescribed in I.P. e.g. chloride, sulphate, arsenic,
lead, iron, nitrate, alkali and alkaline earth metals. 3
4. The theoretical basis and techniques of quantitative analysis, Solute,
solvent, solution, solubility product range, concentration, definition of
normality, molarit, molality, milliequivalence, strong acids and bases, weak acids and bases, buffers, primary and secondary standards, calculation based on stochiometry problems, theory of indicators (both
external and internal indicators), concept of end point.
5
5. Classification of theoretical considerations and applications to
volumetric analysis. 3
6. Acid base titrations in aqueous medium titrations, complexometric
titrations, redox titrations, argentimetric titrations and nonaqueous
titrations with suitable example.
15
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7. Estimation studies of important gases – Oxygen, Nitrogen and Carbon
dioxide.
3
Reference Books
1. A. H. Bekett and J. B. Stanlake, Practical Pharmaceutical Chemistry, 4 th edition, CBS
Publishers and Distributors, 1997.
2. G. H. Jeffery and J. Bassett, Vogels’ Textbook of Quantitative Chemical Analysis, 5 th
Edition, Longman Scientific and Technical, 1989.
3. Indian Pharmacopoeia, British Pharmacopoeia, USP, Martindale.
PHYSICAL PHARMACY – II 3 hrs / Week
S. No. TOPICS Hours
1. Ionic equilibria and buffers: ß Sorensens pH scale, calculation of pH, effect of pH on ß Ionization of weak acids and bases, calculation of ß Fraction unionized, buffers in pharmaceutical and biological
systems, concept of tonicity, isotonic buffer ß Solutions, application of buffers and concept of tonicity in
pharmacy. Problems
4
2. Solubility: ß Solubility of gases in liquids, henrys law and applications
ß Miscible liquids and partially miscible liquids
ß Solubility of solids in liquids, ideal solubility, solubility
parameters and prediction of solubility in regular solutions
ß Partition phenomena and partitioning of weak electrolytes
and its applications
6
3. Chemical Kinetics: ß Molecularity, order of a reaction and specific rate constant ß Zero order, first order and second order reaction.
(Problems) ß Methods to determine order of a reaction ß Energy of activation, Arrhenius equation and application ß Collision theory and transition state theory
ß Accelerated stability studies – concepts and applications
Problems
8
4. Catalysis: ß Definition, types and specificity
2
5. Interfacial phenomena: ß Surface tension, Interfacial tension ß Surface free energy
ß Pressure difference across curved interfaces
ß Measurement of surface and interfacial tensionCapillary rise
method ß Drop weight method ß Du Nuoy tensiometer method ß Spreading of liquids
ß Spreading coefficient ß Adsorption at liquid interfaces
8
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ß Surface active agents
ß Hydrophilic – Lipophilic balance ß Types of monolayers at liquid interfaces
ß Soluble monolayers
ß Gibbs adsorption equation (No derivation) ß Insoluble monolayers and film balance ß Adsorption at solid interfaces
ß Adsorption isotherms
ß Freundlich adsorption isotherm ß Wetting angle and Contact angle
Problems
6. Electromotive force: ß Electrochemical cell ß Types of electrodes
ß Nernst equation and cell emf ß pH meter and Measurement of pH ß Ion sensitive electrodes
ß Oxidation reduction indicators
ß Concentration cells
Problems
3
7. Colloids: ß Classification ß Preparation, colloid properties such as optical
Kinetic and electrical ß Gold number ß Protective colloid ß Schultz Hardy rule.
5
Reference Books
1. P. J. Sinko, “Martin’s Physical Pharmacy and Pharmaceutical Sciences” 5 th edition,
Lippincotts Williams and Wilkin, Indian Edn. Distributed by B. I. Publications Pvt. Ltd., 2006. 2. A. Findlay, “Practical Physical Pharmacy” revised and edited by J. A. Kitchener, 8 th
Edn. Longmans, Green and company Ltd. 1967. 3. B. S. Bahl, A. Bahl, G. D. Tuli, “Essentials of Physical Chemistry ” revised edition, S. Chand and company Ltd., New Delhi, 2006.
4. U. B. Hadkar “A Textbook of Physical Pharmacy”, 6 th Edn. Nirali Prakashan, Pune
2006. 5. U. B. Hadkar, T. N. Vasudevan, K. S. Laddha “Practical Physical Pharmacy” Yucca
Publishing House, Dombivali, 1994.
PHARMACEUTICS – II
S. No. Topic Hours
1. Introduction to per formulation studies with respect to monophasics: ß Organoleptic properties
ß Purity
ß Solubility and techniques of solubilzation ß Partition coefficient and dissociation constant, Salt
formation ß Polymorphism and crystal habit ß Stability and Interaction with excipients.
9
2. Complexion: 2
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ß Types of complexes and their analysis. 3. Formulation, large scale manufacturing, packaging and Quality Control
of nonsterile monophasic liquids: ß Solutions
ß Aromatic waters
ß Syrups
ß Elixirs
ß Linctuses
ß Drops
ß Glycerites
ß Paints
ß Lotions
ß Liniments
ß Sprays.
9
4. Powder Technology: ß Fundamental and derived properties of powders and their
measurement ß Size reduction. ß Size separation.
7
5. Formulation, large scale manufacturing, Packaging and Quality control
of Powders: ß Dusting powders ß Oral rehydration powders
ß Dry syrup formulations.
4
6. Diffusion: ß Fick’s laws and steady state diffusion, measurement of
diffusion.
Dissolution: ß Dissolution rate, Noyes – Whitney equation, Hixon Crowell Law
4
REFERENCE BOOKS:
1. L. V. Allen Jr., N. G. Popovich and H. C. Ansel “Ansel’s Pharmaceutical Dosage
Forms and Drug Delivery S. D. systems”, 8th Edn. Lippincotts Williams and Wilkin.
Indian Edn Distributed by B.I. Publications Pvt. Ltd., 2005.
2. P. J. Sinko,” Martin’s Physical Pharmacy and Pharmaceutical Sciences” 5 th edition,
Lippincotts Williams and Wilkin, Indian Edn. Distributed by B. I. Publications Pvt. Ltd., 2006
3. M. E. Aulton “Pharmaceutics The Science of Dosage form Design” Churchill
Livingston, London, 2002.
4. “Remington The Science and Practice of Pharmacy”, Vol. I and II, 21 st Edn.
Lippincotts Williams and Wilkin, Indian Edn. Distributed by B. I. Publications Pvt. Ltd., 2005
5. E. A. Rowling “Bentleys Textbook of Pharmaceutics” 8 th Edn. Bailliere Tindall London,
Indian Edn. Published by all India Traveler Book seller Delhi, 1992.
6. R. A Lyman and G. Urdang “American Pharmacy” 5 th Edn.
7. James Swarbick “Current concepts in Pharmaceutical Sciences: Dosage form design
and bioavailability” Lea and Febiger, Philadelphia, 1973. 8. S. J Carter “Cooper and Gunn’s Tutorial Pharmacy” 6 th Edn. CBS Publishers and
Distributors, Delhi, 1986. 9. Industrial Pharmacy
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MICROBIOLOGY 3 hrs/ Week
S. No. Topic Hours
1. Brief history of microbiology: Microbiology, scope and application in
pharmaceutical sciences
1
2. Microscopy: Simple microscope, Compound microscope. Resolving power, magnification, angular aperture, and numerical
aperture, oil immersion microscopy to be covered in practical, phase
contrast and dark field.
Fluorescent and electron microscopy.
3
3. Staining (All staining with respect to bacteria):
Monochromatic staining
Gram staining
Acid fast staining
Capsule, flagella spore, cell wall staining
Negative staining
Motility
2
4. Classification of microorganism as different types 1
5. Classification of bacteria:
Morphology, cell characteristic, habitat nutrition Cultivation of bacteria:
Culture media: Cultivation, storage media, enrichment media
differential media, microbiological assay media
Cultivation of aerobes and an aerobes
Pure culture techniques – isolation
Preservation of cultures
Reproduction and Growth phases, measurement of growth, factors
affecting growth, continuous cultivation, enumeration of bacteria
Identification of bacteria
Overview of bacterial diseases in brief
Mycobacterium sp., Salmonella sp., Shigella sp., Staphylococcus
Sp., Klebsiella sp., E.coli., Pseudomonas, Clostridium self study
2
2
2
2
2
2
2
6. Viruses:
Morphological characteristic, enumeration, cultivation and reproduction
HIV and oneogenic Viruses.
3
7. Riekketsiae Diseases 1
8. Fungi:
Morphological characteristics and classification, reproduction, mycosis in brief (Pathogenic fungi like Aspergillus, Dermatophytes. Candida albicans)
2
9. Algae:
Morphological characteristics, reproduction, economic significance of
algae
1
10. Protozoa:
Morphological characteristics and classification, reproduction,
Pathogenic protozoa like Amoeba, Paramecium, Trichomonas, Plasmodium
2
11. Control of microorganisms:
Different techniques of sterilization and their application. Introduction to
aseptic techniques(no equipments to be covered)
Disinfectants and principles of disinfection.
6
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Reference Books:
1. M. J. Pelezar Jr., E. C. S. Chan and N. R. Krieg “Microbiology Concepts and
Applications” McGraw Hill, Inc., USA, 1993. 2. M. Frobisher, R. D. Hinsdill, K. T. Crabtree and C. R. Goodheart “Fundamentals of
Microbiology”, 9 th Edn. Saunders College Publishing, Philadelphia 1968.
3. W. B. Hugo and A. D. Russel “Pharmaceutical Microbiology” 6 th Edn, Blackwell
Science Ltd. UK, 2003. 4. R. Ananthanarayan and Ck. J. Paniker “Test Book of Microbiology”, 7 th Edn. Orient
Longman Pvt. Ltd, Hyderabad, 2005
PHARMACEUTICAL ANALYSIS LABORATORY – I 4hrs/ week
1. Preparation and standardization of 0.1 N HCI, 0.1 N NaOH, 0.1N Na2S2O3, 0.1 N
KMnO4, 0.1 N lodin. 2. Assay of Zinc oxide, Magnesium sulphate, Ferrous sulphate, Potassium iodide,
Copper sulphate. 3. Titrimetric Analysis : Determination of total alkalinity and sodium carbonate of sodium
hydroxide determination of percentage of aspirin, Determination of ascorbic acid
4. Argentimetric titration NaCl powder and KCl. 5. I.P. limit tests for: chloride, sulphate, arsenic, heavy metal, iron.
Reference Books:
1. A. H. Bekett and J. B. Stanlake, Practical Pharmaceutical Chemistry, 4 th edition, CBS
Publishers and Distributors, 1997.
2. G. H. Jeffery and J. Bassett, Vogels’ Textbook of Quantitative: Chemical Analysis, 5 th
Edition. Longman Scientific and Technical 1989.
3. Indian Pharmacopocia, British Pharmacopocia, USP, Martindale
PHARMACEUTICS LAB – I 4hrs/week
List of experiments
Aromatic waters
Chloroform water I.P 66
Concentrated Dill water I.P 66 Concentrated Anise water B.P.C 73
Dill water
Gripe water
Syrups
Syrup I.P 66
Artificial syrup
Cough syrup – Codeine phosphate syrup B.P.C
Linctus
Simple linctus B.P.C
Elixirs
Piperzine citrate elixir B.P.C
Ear drops
Chloramphenicol ear drops B.P.C
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Nasal drops
Ephedrine sulphate nasa drops B.P.C
Glycerites
Glycerin of starch I.P 55
Glycerin of boric acid I.P 55
Glycerin of tannic acid I.P 66
Solutions
Aqueous Iodine solution I.P 66
Weak Iodine solution I.P 66
Paracetamol Solubilised Paediatric drops
Cresol with soap solution I.P
Magnesium citrate oral solution N.F XIV
Chlorinated soda solution, surgical B.P.C
Iodine Paint compound B.P.C 68
Powders
Oral rehydration salt (ORS)
Evaluation of liquids for specific gravity and viscosity and powders for bulk density,
flow rate and angel of repose
PHYSICAL PHARMACY LAB – II 4hrs/week
KINETICS
1. Relative strength. Hydrochloric acid/ sulphuric acid
2. Second order reaction (saponification)
3. Determination of order by equal fraction method (first order reaction )
4. Ostwalds isolation method to determine order
NONKINETICS
1. Parnton coefficient Benzoic acid
2. Surface tension: 1. Determination of surface tension of water, toluene, nhexane, parachor and critical solution temp determination. 2. Determination of CMC
3. Phenol water : Critical solution temp and composition
4. Determination of molecular weight of a polymer from solution viscosity
5. Adsorption : Surface area determination
6. HLB of A surfactant
7. Potentiometer : Titration and determination of bufler capacity
Reference Books:
1. U. B Hadkar, T. N. Vasudevan, K. S. Laddha “Practical Physical Pharmacy” Yucca
Publishing House, Dombivali, 1994.
MICROBIOLOGY LABORATORY 4hrs/ week
1. Study of microscope and common laboratory equipments
2. Gram staining
3. Monochrome staining
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4. Negative staining
5. Cell wall staining
6. Scope staining
7. Capsule staining
8. Motility by hanging drop technique
9. Preparation and sterilization of nutrient broth, agar slants, plates, anoculation
techniques. 10. Isolation of pure culture by pour plate and streak plate methods. Colony
characterization and growth patterns in broth of cocci and bacilli
11. Total count by Breeds smear method
12. Growth by optical density, total plate count
13. Study of yeast, Aspergillus and Penicillum with respect to morphology
14. Observation on prepared slides of malarial parasite in blood smear, intestinal amoeba
in stools.
How do you select a Drug for your M.pharm / Ph.D project based on Lipinski’s rule?
Selection of drug for M.Pharm / Ph.D projects is a very tough task. Getting a New drug itself is a challenging task. Then again there is another problem if the drug you selected is not available in the market. We get a doubt whether the drug is suitable to be made into a tablet or an emulsion. Of course we can know this by bioavailability studies in mice or another animals (maybe humans if the drug is safe) but again how would you feel if at the end of the day you dont get the results you expected?
So before we select a drug for oral use , (this includes not only tablets, capsules, emulsions and suspensions but also novel systems including Liposomes, nanoparticles, Gastro retentive drug delivery systems (GRDDs) and so on,) we need to ensure that our drug satisfies the Lipinski’s rule of Five.
What is Lipinski’s rule of Five
Lipinski’s rule states that, in general, an orally active drug has no more than one violation of the following criteria:
Not more than 5 hydrogen bond donors (nitrogen or oxygen atoms with one or more hydrogen atoms)
Not more than 10 hydrogen bond acceptors (nitrogen or oxygen atoms)
A molecular mass less than 500 daltons
An octanol-water partition coefficient log P not greater than 5
How this rule benefits your project?
The rule describes molecular properties important for a drug’s pharmacokinetics in the human body, including their absorption, distribution, metabolism, and excretion (“ADME”). However, the rule does not predict if a compound is pharmacologically active.
This rule helps Pharmaceutics/Industrial Pharmacy students in proper selection of the drug and knowing whether the drug is suitable for oral formulations.
For Medicinal chemistry students involved in drug designing, CADD, understanding this rule will help you a lot in designing suitable homologues of rugs and fine tuning your drug with suitable modifications
An Example from Lipinski’s original paper
Quoting from Christopher A. Lipinski … “Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings”:
“In the USAN set we found that the sum of Ns and Os in the molecular formula was greater than 10 in 12% of the compounds. Eleven percent of compounds had a MWT of over 500. Ten percent of compounds had a CLogP larger than 5 (or an MLogP larger than 4.15) and in 8% of compounds the sum of OHs and NHs in the chemical structure was larger than 5.
The Lipinski “Rule of Five” states that compounds are likely to have good absorption and permeation in biological systems and are more likely to be successful drug candidates if they meet the following criteria:
five or fewer hydrogen-bond donors
ten or fewer hydrogen-bond acceptors
molecular weight less than or equal to 500
calculated logP less than or equal to 5
*Compound classes that are substrates for biological transporters are exceptions to the rule.
If two parameters are out of range, a “poor absorption or permeability is possible” alert is a very visible educational tool for the chemist and serves as a tracking tool for the research organization.
More Resources
For more information and understanding follow these related resources:
A powerpoint illustrating the basics is here: Lipinski
The original paper of Lipinski is titled “Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings” and is avaialable on Science direct here or here Direct download
There is a page on Facebook (YES!!!) which can be found here
Lipinski Rule-of-5 calculator in ChemDraw/Excel . Get it here or here
