Syllabus for GPAT - 2012

Syllabus for GPAT - 2012

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PHARMACEUTICS

Introduction to Physical pharmacy
Matter, Properties of Matter:
State of matter, change in the state of matter, latent heats and vapor pressure, sublimation-critical point, Eutectic mixtures, gases, aerosols-inhalers, relative humidity, liquid. complexes, liquid crystals, glassy state, solids- crystalline, amorphous and polymorphism.
Micromeretics and Powder Rheology:
Particle size and distribution, average particle size, number and weight distribution, particle number, methods for determining particle volume, methods of determining particle size- optical microscopy, sieving, sedimentation; measurements of particle shape, specific surface area; methods for determining surface area; permeability, adsorption, derived properties of powders, porosity, packing arrangement, densities, bulkiness & flow properties.
Surface and Interfacial Phenomenon:
Liquid interface, surface and interfacial tensions, surface free energy, measurement of surface and interfacial tensions, spreading coefficient, adsorption at liquid interfaces, surface active agents, HLB classification, solubilization, detergency, adsorption at solid interfaces, solid-gas and solid-liquid interfaces, complex films, electrical properties of interface.
Viscosity and Rheology:
Newtonian systems, Law of flow, kinematic viscosity, effect of temperature; non-Newtonian systems: pseudoplastic, dilatant, plastic; thixotropy, thixotropy in formulation, negative thixotropy, determination of viscosity, capillary, falling ball, rotational viscometers.
Dispersion Systems:
Colloidal dispersions: Definition, types, properties of colloids, protective colloids, applications of colloids in pharmacy; Suspensions and Emulsions: Interfacial properties of suspended particles, settling in suspensions, theory of sedimentation, effect of Brownian motion, sedimentation of flocculated particles, sedimentation parameters, wetting of particles, controlled flocculation, flocculation in structured vehicles, rheological considerations; Emulsions-types, theories, physical stability.
Complexation:
Classification of complexes, methods of preparation and analysis, applications.
Kinetics and Drug Stability:
General considerations & concepts, half-life determination, Influence of temperature, light, solvent, catalytic species and other factors, Accelerated stability study, expiration dating.

Importance of microbiology in pharmacy
Structure of bacterial cell; Classification of microbes and their taxonomy:
Actinomycetes, bacteria, rickettsiae, spirochetes and viruses;
Identification of Microbes:
Stains and types of staining techniques, electron microscopy; Nutrition, cultivation, isolation of bacteria, actinomycetes, fungi, viruses, etc; Microbial genetics and variation;
Control of microbes by physical and chemical methods:
Disinfection, factors influencing disinfectants, dynamics of disinfection, disinfectants and antiseptics and their evaluation;
Sterilization:
different methods, validation of sterilization methods & equipments; Sterility testing of all pharmaceutical products. Microbial assays of antibiotics, vitamins & amino acids.

Immunology and Immunological Preparations:
Principles, antigens and heptans, immune system, cellular/humoral immunity, immunological tolerance, antigen-antibody reactions and their applications. Hypersensitivity, active and passive immunization. Vaccines and sera: their preparation, standardization and storage.
Genetic Recombination:
Transformation, conjugation, transduction, protoplast fusion and gene cloning and their applications. Development of hybridoma for monoclonal antibodies. Study of drugs produced by biotechnology such as Activase, Humulin, Humatrope, HB etc;
Antibiotics:
Historical development of antibiotics. Antimicrobial spectrum and methods used for their standardization. Screening of soil for organisms producing antibiotics, fermenter, its design, control of different parameters. Isolation of mutants, factors influencing rate of mutation. Design of fermentation process. Isolation of fermentation products with special reference to penicillins, streptomycins tetracyclines and vitamin B12.

Introduction to pharmaceutical jurisprudence & ethics
Pharmaceutical Legislations:
A brief review; Drugs & Pharmaceutical Industry - A brief review; Pharmaceutical Education - A brief review;
An elaborate study of the followings:
Pharmaceutical Ethics; Pharmacy Act 1948; Drugs and Cosmetics Act 1940 and Rules 1945; Medicinal & Toilet Preparations (Excise Duties) Act 1955; Narcotic Drugs & Psychotropic Substances Act 1985 & Rules; Drugs Price Control Order;
A brief study of the following Acts with special reference to the main provisions and the latest amendments:
Poisons Act 1919; Drugs and Magic Remedies (Objectionable Advertisements) Act 1954; Medical Termination of Pregnancy Act 1970 & Rules 1975; Prevention of Cruelty to Animals Act 1960; States Shops & Establishments Act & Rules; Insecticides Act 1968; AICTE Act 1987; Factories Act 1948; Minimum Wages Act 1948; Patents Act 1970.
A brief study of the various Prescription/Non-prescription Products. Medical/Surgical accessories, diagnostic aids, appliances available in the market.

Introduction to dispensing and community pharmacy
Prescription:
Handling of prescription, source of errors in prescription, care required in dispensing procedures including labeling of dispensed products. General dispensing procedures including labeling of dispensed products; Pharmaceutical calculations: Posology, calculation of doses for infants, adults and elderly patients; Enlarging and reducing recipes percentage solutions, alligation, alcohol dilution, proof spirit, isotonic solutions, displacement value etc;
Principles involved and procedures adopted in dispensing of :
Typical prescriptions like mixtures, solutions, emulsions, creams, ointments, powders, capsules, pastes, jellies, suppositories, ophthalmic, pastilles, lozenges, pills, lotions, liniments, inhalations, paints sprays tablet triturates, etc;
Incompatibilities:
Physical and chemical incompatibilities, inorganic incompatibilities including incompatibilities of metals and their salts, non-metals, acids, alkalis, organic incompatibilities. Purine bases, alkaloids, pyrazolone derivatives, amino acids, quaternary ammonium compounds, carbohydrates, glycosides, anesthetics, dyes, surface active agents, correction of incompatibilities. Therapeutic incompatibilities;
Community Pharmacy:
Organization and structure of retail and whole sale drug store-types of drug store and design, legal requirements for establishment, maintenance and drug store-dispensing of proprietary products, maintenance of records of retail and wholesale, patient counseling, role of pharmacist in community health care and education (First aid, communicable diseases, nutrition, family planning).

Organization and Structure of hospital pharmacy:
Organization of a hospital and hospital pharmacy, Responsibilities of a hospital pharmacist, Pharmacy and therapeutic committee, Budget preparation and Implementation.
Hospital Formulary:
Contents, preparation and revision of hospital formulary.
Drug Store Management and Inventory Control:
Organization of drug store, Types of materials stocked, storage conditions; Purchase and Inventory Control principles, purchase procedures, Purchase order, Procurement and stocking;
Drug distribution Systems in Hospitals:
Out-patient dispensing, methods adopted; Dispensing of drugs to in-patients. Types of drug distribution systems. Charging policy, labeling; Dispensing of drugs to ambulatory patients; Dispensing of controlled drugs, Dispensing of ancillary supplies;
Central Sterile Supply Unit and their Management:
Types of materials for sterilization, Packing of materials prior to sterilization, sterilization equipments, Supply of sterile materials.
Manufacture of Sterile and Non-sterile Products:
Policy making of manufacturable items, demand and costing, personnel requirements, manufacturing practice, Master formula Card, production control, Manufacturing records.
Drug Information Services:
Sources' of Information on drugs, disease, treatment schedules, procurement of information, Computerized services (e.g., MEDLINE), Retrieval of information, Medication error- types of medication errors, correction and reporting.
Records and Reports:
Prescription filling, drug profile, patient medication profile, cases on drug interaction and adverse reactions, idiosyncratic cases. Pharmacoeconomics: Introduction to pharmacoeconomics, different methods of pharmacoeconomics, application of pharmacoeconomics. Pharmacoepidemiology: Definition and scope, method to conduct pharmacoepidemiological studies, advantages & disadvantages of pharmacoepidemiological studies.
Nuclear Pharmacy:
Methods of handling radioisotopes, radioisotope committee.

Importance of unit operations in manufacturing, Stoichiometry:
Unit processes
Material and energy balances, molecular units, mole fraction, tie substance, gas laws, mole volume, primary and secondary quantities, equilibrium state, rate process, steady and unsteady states, dimensionless equations, dimensionless formulae, dimensionless groups, different types of graphic representation, mathematical problems.
Fluid Flow:
Types of flow, Reynold's number, Viscosity, Concept of boundary layer, basic equations of fluid flow, valves, flow meters, manometers and measurement of flow and pressure.
Heat transfer:
Concept of heat flow, applications of Fourier’s law, forced and natural convection, surface coefficients, boiling liquids, condensing vapors, heat exchangers, heat interchangers, radiation, black body, Stefan Boltzmann equation, Kirchoff’s law.
Evaporation:
Basic concept of phase equilibria, factor affecting evaporation, evaporators, film evaporators, single effect and multiple effect evaporators, Mathematical problems on evaporation.
Distillation:
Roult's law, phase diagrams, volatility; simple steam and flash distillations, principles of rectification, Mc-Cabe Thiele method for calculations of number of theoretical plates, Azeotropic and extractive distillation.
Drying:
Moisture content and mechanism of drying, rate of drying and time of drying calculations; classification and types of dryers, dryers used in pharmaceutical industries and special drying methods.
Size Reduction:
Definition, objectives of size reduction, mechanisms of size reduction, factors affecting size reduction, laws governing energy and power requirements of a mills including ball mill, hammer mill, fluid energy mill. Size separation: Different techniques of size separation, sieves, sieve shakers, sedimentation tank, cyclone separators, bag fillers etc.
Mixing:
Theory of mixing, solid-solid, solid-liquid and liquid-liquid mixing equipments.
Filtration and Centrifugation:
Theory of filtration, continuous and batch filters, filter aids, filter media, industrial filters including filter press, rotary filter, edge filter, etc. Factors affecting filtration, filtration, optimum cleaning cycle in batch filters. Principles of centrifugation, industrial centrifugal filters, and centrifugal sedimenters;
Crystallization:
Characteristics of crystals like-purity, size, shape, geometry, habit, forms size and factors affecting them, Solubility curves and calculation of yields. Material and heat balances around Swenson Walker Crystallizer. Supersaturation, theory and its limitations, Nucleation mechanisms, crystal growth. Study of various types of Crystallizers, tanks, agitated batch, Swenson Walker, Single vacuum, circulating magma and Krystal Crystallizer, Caking of crystals and its prevention. Numerical problems on yields;
Dehumidification and Humidity Control:
Basic concepts and definition, wet bulb and adiabatic saturation temperatures, Hygrometric chart and measurement of humidity, application of humidity measurement in pharmacy, equipments for dehumidificat4ion operations;
Refrigeration and Air Conditioning:
Principle and applications of refrigeration and air conditioning;
Material of Construction :
General study of composition, corrosion, resistance, Properties and applications of the materials of construction with special reference to stainless steel and glass.
Material Handling Systems:
Liquid handling - Different types of pumps, Gas handling-Various types of fans, blowers and compressors, Solid handling-Bins, Bunkers, Conveyers, Air transport.
Corrosion:
Classification, mechanism of corrosion, factors affecting, prevention and control.
Plant location:
Layout, utilities and services.
Industrial Hazards and Safety Precautions:
Mechanical, Chemical, Electrical, fire and dust hazards. Industrial dermatitis, Accident records etc.
Automated Process Control Systems:
Process variables, temperature, pressure, flow, level and vacuum and their measurements; elements of automatic process control and introduction to automatic process control systems; elements of computer aided manufacturing (CAM). Reactors and fundamentals of reactors design for chemical reactions.

Dosages Forms, designing & evaluation
Liquid Dosages Forms:
Introduction, types of additives used in formulations, vehicles, stabilizers, preservatives, suspending agents, emulsifying agents, solubilizers, colors, flavors and others, manufacturing packaging, labeling, evaluation of clear liquids, suspensions and emulsions official in pharmacopoeia;
Semisolid Dosage Forms:
Definitions, types, mechanisms of drug penetration, factors influencing penetration, semisolid bases and their selection. General formulation of semisolids, clear gels manufacturing procedure, evaluation and packaging;
Suppositories:
Ideal requirements, bases, displacement value, manufacturing procedure, packaging and evaluation;
Extraction and Galenical Products:
Principle and method of extraction, preparation of infusion, tinctures, dry and soft liquid extracts;
Blood Products and Plasma Substitutes:
Collection, processing and storage of whole human blood, concentrated human RBCs, dried human plasma, human fibrinogen, human thrombin, human normal immunoglobulin, human fibrin, foam plasma substitutes, -ideal requirements, PVP, dextran etc. for control of blood pressure as per I.P.;
Pharmaceutical Aerosols:
Definition, propellants, general formulation, manufacturing' and packaging methods, pharmaceutical applications;
Ophthalmic Preparations:
Requirements, formulation, methods of preparation, labeling, containers, evaluation;
Cosmeticology and Cosmetic Preparations:
Fundamentals of cosmetic science, structure and functions of skin and hair. Formulation, preparation and packaging of cosmetics for skin, hair, dentifrice and manicure preparations like nail polish, nail polish remover, Lipsticks, eye lashes, baby care products etc.
Capsules:
Advantages and disadvantages of capsule dosage form, material for production of hard gelatin capsules, size of capsules, formulation, method of capsule filling, soft gelatin, capsule shell and capsule content, importance of base absorption and minimum/gm factors in soft capsules, quality control, stability testing and storage of capsule dosage forms.
Micro-encapsulation:
Types of microcapsules, importance of microencapsulation in pharmacy, microencapsulation by phase separation, coacervation, multi-orifice, spray drying, spray congealing, polymerization complex emulsion, air suspension technique, coating pan and other techniques, evaluation of micro capsules.
Tablets:
Advantages and disadvantages of tablets, Application of different types of tablets, Formulation of different types of tablets, granulation, technology on large-scale by various techniques, different types of tablet compression machinery and the equipments employed, evaluation of tablets. Coating of Tablets: Types of coating, film forming materials, formulation of coating solution, equipments for coating, coating process, evaluation of coated tablets. Stability kinetics and quality assurance.
Parenteral Products:
Pre-formulation factors, routes of administration, water for injection, and sterile water for injection, pyrogenicity, non aqueous vehicles, isotonicity and methods of its adjustment, Formulation details, Containers and closures and selection, labeling; Pre-filling treatment, washing of containers and closures, preparation of solution and suspensions, filling and closing of ampoules, vials, infusion fluids, lyophilization & preparation of sterile powders, equipment for large scale manufacture and evaluation of parenteral products; Aseptic Techniques-source of contamination and methods of prevention, Design of aseptic area, Laminar flow bench services and maintenance. Sterility testing of pharmaceuticals.
Surgical products:
Definition, primary wound dressing, absorbents, surgical cotton, surgical gauzes etc., bandages, adhesive tape, protective cellulosic hemostastics, official dressings, absorbable and non-absorbable sutures, ligatures and catguts.
Packaging of Pharmaceutical Products:
Packaging components, types, specifications and methods of evaluation, stability aspects of packaging. Packaging equipments, factors influence choice of containers, legal and official requirements for containers, package testing.

Designing of dosage forms:
Pre-formulation studies, Study of physical properties of drug like physical form, particle size, shape, density, wetting, dielectric constant. Solubility, dissolution and organoleptic properties and their effect on formulation, stability and bioavailability. Study of chemical properties of drugs like hydrolysis, oxidation, reduction, racemization, polymerization etc., and their influence on formulation and stability of products. Study of pro-drugs in solving problems related to stability, bioavailability and elegancy of formulations. Design, development and process validation methods for pharmaceutical operations involved in the production of pharmaceutical products with special reference to tablets, suspensions. Stabilization and stability testing protocol for various pharmaceutical products. ICH Guidelines for stability testing of formulations.
Performance evaluation methods:
In-vitro dissolution studies for solid dosage forms methods, interpretation of dissolution data. Bioavailability studies and bioavailability testing protocol and procedures. In vivo methods of evaluation and statistical treatment. GMP and quality assurance, Quality audit. Design, development, production and evaluation of controlled/sustained/extended release formulations.

Biopharmaceutics & Pharmacokinetcs
Introductiont to biopharmaceutics:
Passage of drugs across biological barrier (passive diffusion, active transport, facilitated diffusion, ion-pair formation and pinocytosis); Factors influencing absorption- biological, physico-chemical, physiological and pharmaceutical; Drug distribution in the body, plasma protein binding.
Pharmacokinetics:
Significance of plasma drug concentration measurement. Compartment model- Definition and Scope. Pharmacokinetics of drug absorption - Zero order and first order absorption rate constant using Wagner-Nelson and residual methods. Volume of distribution and distribution coefficient. Compartment kinetics- One compartment and two compartment models. Determination of pharmacokinetic parameters from plasma and urine data after drug administration by intravascular and oral route. Clearance concept, mechanism of renal clearance, clearance ratio, determination of renal clearance. Extraction ratio, hepatic clearance, biliary excretion, extra-hepatic circulation. Non-linear pharmacokinetics with special reference to one compartment model after I.V. drug administration.
Clinical Pharmacokinetics:
Definition and scope: Dosage adjustment in patients with and without renal and hepatic failure; Design of single dose bio-equivalence study and relevant statistics; Pharmacokinetic drug interactions and their significance in combination therapy.
Bioavailability and bioequivalence:
Measures of bioavailability, Cmax, tmax, Keli and Area Under the Curve (AUC); Design of single dose bioequivalence study and relevant statistics; Review of regulatory requirements for conducting bioequivalent studies. Biopharmaceutical Classification System (BCS) of drugs.

PHARMACEUTICAL CHEMISTRY

Inorganic pharmaceutical & medicinal chemistry
Importance of inorganic compounds in pharmacy and medicine;
An outline of methods of preparation, uses, sources of impurities, tests for purity and identity, including limit tests for iron, arsenic, lead, heavy metals, chloride, sulphate and special tests if any, of the following classes of inorganic pharmaceuticals included in Indian Pharmacopoeia:
Gastrointestinal Agents:
Acidifying agents, Antacids, Protectives and Adsorbents, Cathartics;
Major Intra- and Extra-cellular Electrolytes:
Physiological ions. Electrolytes used for replacement therapy, acid-base balance and combination therapy;
Essential and Trace Elements:
Transition elements and their compounds of pharmaceutical importance, Iron and haematinics, mineral supplements; Cationic and anionic components of inorganic drugs useful for systemic effects;
Topical Agents:
Protectives, Astringents and Anti-infectives;
Gases and Vapors:
Oxygen, Anesthetics (inorganic) and Respiratory stimulants;
Dental Products:
Dentifrices, Anti-caries agents; Complexing and chelating agents used in therapy;
Miscellaneous Agents:
Sclerosing agents, Expectorants, Emetics, Inorganic poisons and antidotes.
Pharmaceutical Aids Used in Pharmaceutical Industry:
Anti-oxidants, Preservatives, Filter aids, Adsorbents, Diluents, Excipients, Suspending agents, Colorants;
Acids, Bases and Buffers:
Buffer equations and buffer capacity in general, buffers in pharmaceutical systems, preparation, stability, buffered isotonic solutions, measurements of tonicity, calculations and methods of adjusting isotonicity. Water;
Inorganic Radiopharmaceuticals:
Nuclear reaction, radioisotopes, radiopharmaceuticals, Nomenclature, Methods of obtaining their standards and units of activity, half-life, measurement of activity, clinical applications, dosage, hazards and precautions.

Physical Chemistry and its importance in pharmacy
Importance of basic fundamentals of physical chemistry in pharmacy:
Behaviour of Gases, Kinetic theory of gases, deviation from ideal behavior and explanation;
The Liquid State:
Physical properties (surface tension, parachor, viscosity, refractive index, dipole moment);
Solutions:
Ideal and real solutions, solutions of gases in liquids, colligative properties, partition coefficient, conductance and its measurement, Debye Huckel theory;
Thermodynamics:
First, Second and Third laws, Zeroth law, Concept of free energy, enthalpy and entropy, absolute temperature scale;
Thermochemical equations; Phase rule; Adsorption:
Freudlich and Gibbs adsorption, isotherms, Langmuir’s theory of adsorption;
Photochemistry:
Consequences of light absorption, Jabolenski diagram, Quantum efficiency;
Chemical Kinetics:
Zero, First and Second order reactions, complex reactions, theories of reaction kinetics, characteristics of homogeneous and heterogeneous catalysis, acid base and enzyme catalysis;
Quantum Mechanics :
Postulates of quantum mechanics, operators in quantum mechanics, the Schrodinger wave equation.

Organic Chemistry and its importance in pharmacy
Importance of fundamentals of organic chemistry in pharmaceutical sciences; Structure and Properties:
Atomic structure, Atomic orbitals, Molecular orbital theory, wave equation, Molecular orbitals, Bonding and Anti-bonding orbitals, Covalent bond, Hybrid orbitals, Intramolecular forces, Bond dissociation energy, Polarity of bonds, Polarity of molecules, Structure and physical properties, Intermolecular forces, Acids and bases;
Stereochemistry:
Nomenclature, isomerism, stereoisomerism, conformational and configurational isomerism, optical activity, specification of configuration, Reactions involving stereoisomers, chirality, conformations;
Stereoselective and stereospecific reactions; Structure, Nomenclature, Preparation and Reactions of:
Alkanes, Alkenes, Alkynes, Cyclic analogs, Dienes, Benzene, Polynuclear aromatic compounds, Arenes, Alkyl halides, Alcohols, Ethers, Epoxides, Amines, Phenols, Aldehydes and ketones, Carboxylic acids, Functional derivatives of' carboxylic acids, a,ß-Unsaturated carbonyl compounds, Reactive intermediates- carbocations, carbanions, carbenes and nitrenes;
Nucleophilic and Electrophilic Aromatic Substitution Reactions:
Reactivity and orientation;
Electrophilic and Nucleophilic Addition Reactions; Rearrangements
(Beckman, Hoffman, Benzilic acid, pinacole-pinacolone and Beyer-Villiger);
Elimination reactions; Conservation of Orbital Symmetry and Rules:
Electrocyclic, Cycloaddition and Sigmatropic reactions;
Neighboring group effects; Catalysis by transition metal complexes; Heterocyclic Compounds:
Nomenclature, preparation, properties and reactions of 3, 4, 5, 6 & 7-membered heterocycles with one or two heteroatoms like 0, N, S. Chemistry of lipids, Carbohydrates and Proteins.

Biochemistry
Biochemistry in pharmaceutical sciences:
The concept of free energy, Determination of change in free energy - from equilibrium constant and reduction potential, bioenergetics, production of ATP and its biological significance;
Enzymes:
Nomenclature, enzyme kinetics and their mechanism of action, mechanism of inhibition, enzymes and iso-enzymes in clinical diagnosis;
Co-enzymes:
Vitamins as co-enzymes and their significance. Metals as cofactors and their significance; Carbohydrate Metabolism: Conversion of polysaccharides to glucose-1-phosphate, Glycolysis, fermentation and their regulation, Gluconeogenesis and glycogenolysis, Metabolism of galactose and galactosemia, Role of sugar nucleotides in biosynthesis, and Pentose phosphate pathway;
The Citric Acid Cycle:
Significance, reactions and energetics of the cycle, Amphibolic role of the cycle, and Glyoxalic acid cycle;
Lipids Metabolism :
Oxidation of fatty acids, ß-oxidation & energetics, biosynthesis of ketone bodies and their utilization, biosynthesis of saturated and unsaturated fatty acids, Control of lipid metabolism, Essential fatty acids & eicosanoids (prostaglandins, thromboxanes and leukotrienes), phospholipids, and sphingolipids, Biosynthesis of eicosanoids, cholesterol, androgens, progesterone, estrogens corticosteroids and bile acids;
Biological Oxidation:
Redox-potential, enzymes and co-enzymes involved in oxidation reduction & its control, The respiratory chain, its role in energy capture and its control, energetics of oxidative phosphorylation. Inhibitors of respiratory chain and oxidative phosphorylation, Mechanism of oxidative phosphorylation;
Metabolism of ammonia and nitrogen containing monomers:
Nitrogen balance, Biosynthesis of amino acids, Catabolism of amino acids, Conversion of amino acids to specialized products, Assimilation of ammonia, Urea. cycle, metabolic disorders of urea cycle, Metabolism of sulphur containing amino acids;
Purine biosynthesis:
Purine nucleotide inter-conversions;
Pyrimidine biosynthesis:
and formation of deoxyribounucleotides;
Biosynthesis of Nucleic Acids:
Brief introduction of genetic organization of the mammalian genome, alteration and rearrangements of genetic material, Biosynthesis of DNA and its replications;
Mutation:
Physical & chemical mutagenesis/carcinogenesis, DNA repair mechanism. Biosynthesis of RNA;
Genetic Code and Protein Synthesis:
Genetic code, Components of protein synthesis and Inhibition of protein synthesis.

Medicinal Chemistry
Basic Principles:
Physico-chemical and stereoisomeric (Optical, geometrical) aspects of drug molecules and biological action, Bioisosterism, Drug-receptor interactions including transduction mechanisms;
Drug metabolism and Concept of Prodrugs; Principles of Drug Design (Theoretical Aspects):
Traditional analog and mechanism based approaches, QSAR approaches, Applications of quantum mechanics, Computer Aided Drug Designing (CADD) and molecular modeling;
Synthetic Procedures, Mode of Action, Uses, Structure Activity Relationships including Physicochemical Properties of the Following Classes of Drugs:
Drugs acting at synaptic and neuro-effector junction sites: Cholinergics, anti-cholinergics and cholinesterase inhibitors, Adrenergic drugs, Antispasmodic and anti-ulcer drugs, Local Anesthetics, Neuromuscular blocking agents;
Autacoids:
Antihistamines, Eicosanoids, Analgesic-antipyretics, Anti-inflammatory (non-steroidal) agents.
Steroidal Drugs:
Steroidal nomenclature (IUPAC) and stereochemistry, Androgens and anabolic agents, Estrogens and Progestational agents, Oral contraceptives, Adrenocorticoids;
Drugs acting on the central nervous system:
General Anesthetics, Hypnotics and Sedatives, Anticonvulsants, Anti-Parkinsonian drugs, Psychopharmacological agents (Neuroleptics, Anti-depressants, Anxiolytics), Opioid analgesics, Anti-tussives, CNS stimulants;
Diuretics; Cardiovascular drugs:
Anti-hypertensives, Anti-arrythmic agents, anti-anginal agents, Cardiotonics, Anti-hyperlipedemic agents, Anticoagulants and Anti-platelet drugs;
Thyroid and Anti thyroid drugs; Insulin and oral hypoglycemic agents;
Chemotherapeutic Agents used in bacterial, fungal, viral, protozoal, parasitic and other infections, Antibiotics: ß-Lactam, macrolides, tetracyclines, aminoglycosides, polypeptide antibiotics, fluoroquinolones,
Anti-metabolites
(including sulfonamides); Anti-neoplastic agents; Anti-viral agents (including anti–HIV);
Immunosuppressives and immunostimulants; Diagnostic agents; Pharmaceutical Aids; Microbial Transformations:
Introduction, types of reactions mediated by micro-organisms, design of biotransformation processes, selection of organisms, biotransformation process and its improvements with special reference to steroids;
Enzyme Immobilization:
Techniques of immobilization, factors affecting enzyme kinetics, Study of enzymes such as hyaluronidase, penicillinase, streptokinase, amylases and proteases, Immobilization of bacteria and plant cells.
Different techniques of pharmaceutical analysis, Preliminaries and definitions:
Significant figures, Rules for retaining significant digits, Types of errors, Mean deviation, Standard deviation, Statistical treatment of small data sets, Selection of sample, Precision and accuracy,

Pharmaceutical Analysis
Fundamentals of volumetric analysis:
methods of expressing concentration, primary and secondary standards:
Acid Base Titrations:
Acid base concepts, Role of solvents, Relative strengths of acids and bases, Ionization, Law of mass action, Common ion effect, Ionic product of water, pH, Hydrolysis of salts, Henderson-Hasselbach equation, Buffer solutions, Neutralization curves, Acid-base indicators, Theory of indicators, Choice of indicators, Mixed indicators, Polyprotic systems, Polyamine and amino acid systems, Amino acid titrations;
Oxidation Reduction Titrations:
Concepts of oxidation and reduction, Redox reactions, Strengths and equivalent weights of oxidizing and reducing agents, Theory of redox titrations, Redox indicators, Cell representations, Measurement of electrode potential, Oxidation-reduction curves, Iodimetry and Iodometry, Titrations involving cerric ammonium sulphate, potassium iodate, potassium bromate, potassium permanganate; titanous chloride, stannous chloride and Sodium 2,6-dichlorophenolindophenol;
Precipitation Titrations:
Precipitation reactions, Solubility product, Effect of acids, temperature and solvent upon the solubility of a precipitate, Argentometric titrations and titrations involving ammonium or potassium thiocyanate, mercuric nitrate, and barium sulphate, indicators, Methods of end point determination (GayLussac method, Mohr’s method, Volhard's method and Fajan's method).
Gravimetric Analysis:
Precipitation techniques, The colloidal state, Supersaturation, Co-precipitation, Post-precipitation, Digestion, washing of the precipitate, Filtration, Filter papers and crucibles, Ignition, Thermogravimetric curves, Specific examples like barium sulphate, aluminium as aluminium oxide, calcium as calcium oxalate and magnesium as magnesium pyrophosphate, Organic precipitants;
Non-aqueous titrations:
Acidic and basic drugs, Solvents used, Indicators;
Complexometric titrations;
Complexing agents used as titrants, Indicators, Masking and demasking;
Miscellaneous Methods of Analysis:
Diazotization titrations, Kjeldahl method of nitrogen estimation, Karl-Fischer aquametry, Oxygen flask combustion method, Gasometry;
Extraction procedures including separation of drugs from excipients; Potentiometry:
Standard redox potential, Nernst equation, Half-cell potential, Standard and indicating electrodes, potentiometric titrations;
Conductometry:
Specific and equivalent conductance, conductometric titrations;
Coulometry:
Coulomb’s law, Coulometric titrations at fixed potential/current;
Polarography:
Decomposition potential, Half-wave potential, Diffision/migration/migration current, Ilkovic equation, Cathodic/anodic polarography, Dropping mercury electrode, Graphite electrode, Organic polarography;
Amperometry:
Rotating platinum electrode, Amperometric titrations;
Chromatography:
Theory of chromatography, plate theory, Factors affecting resolution, van Deemter equation, The following chromatographic techniques (including instrumentation) with relevant examples of Pharmacopoeial products: TLC, HPLC, GLC, HPTLC, Paper Chromatography and Column Chromatography;
The Theoretical Aspects, Basic Instrumentation, Elements of Interpretation of Spectra, and Applications (quantitative and qualitative) of the Following Analytical Techniques:
Ultraviolet and visible spectrophotometry, Fluorimetry, Infrared spectrophotometry, Nuclear Magnetic Resonance spectroscopy, Mass Spectrometry (EI & CI only), Flame Photometry, Atomic Absorption Spectroscopy, X-ray Diffraction Analysis, Radioimmunoassay.
Quality assurance:
GLP, ISO 9000, TQM, Quality Review and Quality documentation, Regulatory control, regulatory drug analysis, interpretation of analytical data, Validation, quality audit: quality of equipment, validation of equipment, validation of analytical procedures.

PHARMACOLOGY

Pathophysiology of common diseases; Basic Principles of Cell Injury and Adaptations:
Causes of Cellular injury, pathogenesis, morphology of cell injury, adaptations and cell death.
Basic Mechanisms involved in the process of inflammation and repair:
Vascular and cellular events of acute inflammation, chemical mediators of inflammation, pathogenesis of chronic inflammation, brief outline of the process of repair.
Immunopathophysiology:
T and B cells, MHC proteins, antigen presenting cells, immune tolerance, pathogenesis of hypersensitivity reactions, autoimmune diseases, AIDS, Amyloidosis.
Pathophysiology of Common Diseases:
Asthma, diabetes, rheumatoid arthritis, gout, ulcerative colitis, neoplasia, psychosis, depression, mania, epilepsy, acute and chronic renal failure, hypertension, angina, congestive heart failure, atherosclerosis, myocardial infarction, congestive heart failure, peptic ulcer, anemias, hepatic disorders, tuberculosis, urinary tract infections and sexually transmitted diseases. Wherever applicable the molecular basis should be discussed.

Fundamentals of general pharmacology:
Dosage forms and routes of administration, mechanism of action, combined effect of drugs, factors modifying drug action, tolerance and dependence; Pharmacogenetics; Principles of Basic and Clinical pharmacokinetics, absorption, Distribution, Metabolism and Excretion of drugs, Adverse Drug Reactions; Bioassay of Drugs and Biological Standardization; Discovery and development of new drugs, Bioavailability and bioequivalence studies;
Pharmacology of Peripheral Nervous System:
Neurohumoral transmission (autonomic and somatic), Parasympathomimetics, Parasympatholytics, Sympathomimetics, Adrenergic receptor and neuron blocking agents, Ganglion stimulants and blocking agents, Neuromuscular blocking Agents, Local anesthetic Agents.
Pharmacology of Central Nervous System:
Neurohumoral transmission in the C.N.S., General Anesthetics, Alcohols and disulfiram, Sedatives, Hypnotics, Anti-anxiety agents and Centrally acting muscle relaxants, Psychopharmacological agents (anti-psychotics), anti-maniacs and hallucinogens, Antidepressants, Anti-epileptics drugs, Anti-Parkinsonian drugs, Analgesics, Antipyretics, Narcotic analgesics and antagonists, C.N.S. stimulants, Drug Addiction and Drug Abuse.
Pharmacology of Cardiovascular System:
Drugs used in the management of congestive cardiac failure, Antihypertensive drugs, Anti-anginal and Vasodilator drugs, including calcium channel blockers and beta adrenergic antagonists, Anti-arrhythmic drugs, Anti-hyperlipedemic drugs, Drugs used in the therapy of shock.
Drugs Acting on the Hemopoietic System:
Hematinics, Anticoagulants, Vitamin K and hemostatic agents, Fibrinolytic and anti-platelet drugs, Blood and plasma volume expanders.
Drugs acting on urinary system:
Fluid and electrolyte balance, Diuretics.
Autacoids:
Histamine, Antihistaminic drugs, 5-HT- its agonists and antagonists, Prostaglandins, thromboxanes and leukotrienes, Angiotensin, Bradykinin and Substance P and other vasoactive peptides, non-steroidal anti-inflammatory and anti-gout agents.
Drugs Acting on the Respiratory System:
Anti-asthmatic drugs including bronchodilators, Anti-tussives and expectorants, Respiratory stimulants.
Drugs acting on the Gastrointestinal Tract:
Antacids, Anti-secretory and Anti-ulcer drugs, Laxatives and anti-diarrhoeal drugs, Appetite Stimulants and Suppressants, Emetics and anti-emetics, Miscellaneous: Carminatives, demulcents, protectives, adsorbents, astringents, digestants, enzymes and mucolytics.
Pharmacology of Endocrine System:
Hypothalamic and pituitary hormones, Thyroid hormones and anti thyroid drugs, parathormone, calcitonin and Vitamin D, Insulin, glucagons, incretins, oral hypoglycemic agents and insulin analogs, ACTH and corticosteroids, Androgens and anabolic steroids, Estrogens, progesterone and oral contraceptives, Drugs acting on the uterus.
Chemotherapy:
General Principles of Chemotherapy, Bacterial resistance; Sulfonamides and cotrimoxazole, Antibiotics- Penicillins, Cephalosporins, Aminoglycosides, Chloramphenicol, Macrolides, Tetracyclines, Quinolones, fluoroquinolones and Miscellaneous antibiotics; Chemotherapy of tuberculosis, leprosy, fungal diseases, viral diseases, HIV and AIDS, urinary tract infections and sexually transmitted diseases, malaria, amoebiasis and other protozoal infections and Anthelmentics. Chemotherapy of malignancy and immunosuppressive agents.
Principles of Toxicology:
Definition of poison, general principles of treatment of poisoning with particular reference to barbiturates, opioids, organophosphorous and atropine poisoning, Heavy metals and heavy metal antagonists.

Basic Concepts of Pharmacotherapy:
Clinical Pharmacokinetics and individualization of Drug therapy, Drug delivery systems and their Biopharmaceutic & Therapeutic considerations, Drugs used during infancy and in the elderly persons (Pediatrics & Geriatrics), Drugs used during pregnancy, Drug induced diseases, The basics of drug interactions, General principles of clinical toxicology, Common clinical laboratory tests and their interpretation;
Important Disorders of Organs, Systems and their Management:
Cardio-vascular disorders- Hypertension, Congestive heart failure, Angina, Acute myocardial infarction, Cardiac arrhythmias.
CNS Disorders:
Epilepsy, Parkinsonism, Schizophrenia,
Depression Respiratory disease-
Asthma.
Gastrointestinal Disorders-
Peptic ulcer, Ulcerative colitis, Hepatitis, Cirrhosis.
Endocrine Disorders-
Diabetes mellitus and Thyroid disorders.
Infectious Diseases-
Tuberculosis, Urinary tract infections, Enteric infections, Upper respiratory infections. Hematopoietic Disorders- Anemias,
Joint and Connective tissue disorders-
Rheumatic diseases, Gout and Hyperuricemia.
Neoplastic Diseases-
Acute Leukaemias, Hodgkin's disease. Therapeutic Drug Monitoring, Concept of Essential Drugs and Rational Drug use.

PHARMACOGNOSY

Sources of Drugs:
Biological, marine, mineral and plant tissue cultures as sources of drugs;
Classification of Drugs:
Morphological, taxonomical, chemical and pharmacological classification of drugs;
Study of medicinally important plants belonging to the families with special reference to:
Apocynacae, Solanaceae, Rutacease, Umbelliferae, Leguminosae, Rubiaceae, Liliaceae, Graminae, Labiatae, Cruciferae, Papaveraceae;
Cultivation, Collection, Processing and Storage of Crude Drugs:
Factors influencing cultivation of medicinal plants, Types of soils and fertilizers of common use. Pest management and natural pest control agents, Plant hormones and their applications, Polyploidy, mutation and hybridization with reference to medicinal plants.
Quality Control of Crude Drugs:
Adulteration of crude drugs and their detection by organoleptic, microscopic, physical, chemical and biological methods and properties.
Introduction to Active Constituents of Drugs:
Their isolation, classification and properties.
Systematic pharmacognostic study of the followings:
CARBOHYDRATES and derived products:
agar, guar gum acacia, Honey, Isabagol, pectin, Starch, sterculia and Tragacanth;
Lipids:
Bees wax, Castor oil, Cocoa butter, Codliver oil, Hydnocarpus oil, Kokum butter, Lard, Linseed oil, Rice, Bran oil, Shark liver oil and Wool fat;
RESINS:
Study of Drugs Containing Resins and Resin Combinations like Colophony, podophyllum, jalap, cannabis, capsicum, myrrh, asafoetida, balsam of Tolu, balsam of Peru, benzoin, turmeric, ginger;
TANNINS:
Study of tannins and tannin containing drugs like Gambier, black catechu, gall and myrobalan;
VOLATILE OILS:
General methods of obtaining volatile oils from plants, Study of volatile oils of Mentha, Coriander, Cinnamon, Cassia, Lemon peel, Orange peel, Lemon grass, Citronella, Caraway, Dill, Spearmint, Clove, Fennel, Nutmeg, Eucalyptus, Chenopodium, Cardamom, Valerian, Musk, Palmarosa, Gaultheria, Sandal wood;
Phytochemical Screening:
Preparation of extracts, Screening of alkaloids, saponins, cardenolides and bufadienolides, flavonoids and leucoanthocyanidins, tannins and polyphenols, anthraquinones, cynogenetic glycosides, amino acids in plant extracts;
FIBERS:
Study of fibers used in pharmacy such as cotton, silk, wool, nylon, glass-wool, polyester and asbestos.

Study of the biological sources, cultivation, collection, commercial varieties, chemical constituents, substitutes, adulterants, uses, diagnostic macroscopic and microscopic features and specific chemical tests of following groups of drugs:

GLYCOSIDE CONTAINING DRUGS:
Saponins :
Liquorice, ginseng, dioscorea, sarsaparilla, and senega.
Cardioactive glycosides:
Digitalis, squill, strophanthus and thevetia,
Anthraquinone cathartics:
Aloe, senna, rhubarb and cascara,
Others:
Psoralea, Ammi majus, Ammi visnaga, gentian, saffron, chirata, quassia.
ALKALOID CONTAINING DRUGS:
Pyridine-piperidine:
Tobacco, areca and lobelia.
Tropane:
Belladonna, hyoscyamus, datura, duboisia, coca and withania.
Quinoline and Isoquinoline:
Cinchona, ipecac, opium.
Indole:
Ergot, rauwolfia, catharanthus, nux-vomica and physostigma.
Imidazole:
Pilocarpus.
Steroidal:
Veratrum and kurchi.
Alkaloidal Amine:
Ephedra and colchicum.
Glycoalkaloid:
Solanum.
Purines:
Coffee, tea and cola. Biological sources, preparation, identification tests and uses of the following enzymes: Diastase, papain, pepsin, trypsin, pancreatin.

Studies of Traditional Drugs:
Common vernacular names, botanical sources, morphology, chemical nature of chief constituents, pharmacology, categories and common uses and marketed formulations of following indigenous drugs: Amla, Kantkari, Satavari, Tylophora, Bhilawa, Kalijiri, Bach, Rasna, Punamava, Chitrack, Apamarg, Gokhru, Shankhapushpi, Brahmi, Adusa, Atjuna, Ashoka, Methi, Lahsun, Palash, Guggal, Gymnema, Shilajit, Nagarmotha and Neem. The holistic concept of drug administration in traditional systems of medicine. Introduction to ayurvedic preparations like Arishtas, Asvas, Gutikas, Tailas, Chumas, Lehyas and Bhasmas.

General Techniques of Biosynthetic Studies and Basic Metabolic Pathways/Biogenesis:
Brief introduction to biogenesis of secondary metabolites of pharmaceutical importance.
Terpenes:
monoterpenes, sesquiterpenes, diterpenes, and triterpenoids.
Carotenoids:
a-carotenoids, ß-carotenes, vitamin A, Xanthophylls of medicinal importance.
Glycosides:
Digitoxin, digoxin, hecogenin, sennosides, diosgenin and sarasapogenin.
Alkaloids:
Atropine and related compounds, Quinine, Reserpine, Morphine, Papaverine, Ephedrine, Ergot and Vinca alkaloids.
Lignans, quassanoids and flavonoids. Role of plant-based drugs on National economy:
A brief account of plant based industries and institutions involved in work on medicinal and aromatic plants in India. Utilization and production of phyto-constituents such as quinine, calcium sennosides, podophyllotoxin, diosgenin, solasodine, and tropane alkaloids. Utilization of aromatic plants and derived products with special reference to sandalwood oil, mentha oil, lemon grass oil, vetiver oil, geranium oil and eucalyptus oil. World-wide trade in medicinal plants and derived products with special reference to diosgenin (disocorea), taxol (Taxus sps) digitalis, tropane alkaloid containing plants, Papain, cinchona, Ipecac, Liquorice, Ginseng, Aloe, Valerian, Rauwolfia and plants containing laxatives. Plant bitters and sweeteners.
Plant Tissue Culture:
Historical development of plant tissue culture, types of cultures, nutritional requirements, growth and their maintenance. Applications of plant tissue culture in pharmacognosy.
Marine pharmacognosy:
Novel medicinal agents from marine sources.
Natural allergens and photosensitizing agents and fungal toxins. Herbs as health foods. Herbal cosmetics. Standardization and quality control of herbal drugs, WHO guidelines for the standardization of herbal drugs.

‎10 imp drug interactions:

‎10 imp drug interactions:

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1)Fluoxetine and Phenelzine
The interaction can result in a central serotonin syndrome.(3)This condition is characterized by mental status changes, agitation, diaphoresis, tachycardia, and death. These symptoms can develop quickly with only 1 or 2 doses of fluoxetine when combined with phenelzine. Serotonin syndrome is possible with any monoamine oxidase inhibitor (MAOI), such as phenelzine or tranylcypromine sulfate, in combination with any drug that increases serotonin levels, such as dextromethorphan, meperidine, and other selective serotonin reuptake inhibitors (SSRIs).(3)It is recommended that fluoxetine be stopped for at least 5 weeks before an MAOI is prescribed because of the long half-life of fluoxetine and its primary metabolite, norfluoxetine. Also, 2 weeks should be allowed after discontinuation of an MAOI before starting SSRI treatment.(3)

2)Digoxin and Quinidine
This significant drug interaction has been known for a long time, yet it continues to be a problem, often with devastating results. The interaction can lead to a marked increase in plasma concentration levels of digoxin in more than 90% of patients.(4)Significant changes in serum digoxin are noticed within 24 hours. The average increase is roughly 2-fold.(5)The effects from this interaction range from nausea and vomiting to death. The primary mechanism for this interaction is a decreased volume of distribution of digoxin, secondary to its displacement from binding sites in body tissues.(4)Quinidine also decreases renal and nonrenal excretion rates of digoxin, which leads to increased steady-state concentrations of the cardiac glycoside.(4)Ideally, patients taking digoxin should avoid the use of quinidine; however, if the combination is necessary, the patient should be closely watched. Pharmacists should anticipate the need to reduce the digoxin dose by one half.(4)

3)Sildenafil and Isosorbide Mononitrate 
Sildenafil may markedly increase the hypotensive effects of isosorbide mononitrate.(6)More than 123 deaths have been reported since 1998, when sildenafil was made available in the United States.(6)Most deaths were among patients with 1 or more risk factors, including obesity, hypertension, and cigarette smoking. Sildenafil was developed as a phosphodiesterase-5 (PDE5) inhibitor. In the presence of PDE5 inhibitors, nitrates can cause intense increases in cyclic guanosine monophosphate and dramatic drops in blood pressure.(7)Patients taking isosorbide mono-nitrate or any nitrate, including nitroglycerin, should be advised not to take sildenafil.

4)Potassium Chloride and Spironolactone
This is another significant drug interaction that has been known for a long time. The combination may result in hyperkalemia.(8)The resulting hyperkalemia can be serious and may lead to cardiac failure and death. Patients with renal impairment are especially prone to this effect. Spironolactone is a competitive antagonist of mineral corticoids, of which aldosterone is a potent example.(9)This mechanism occurs in the kidney at the distal portion of the nephron and leads to the excretion of sodium ions while saving potassium ions.(9)Patients receiving potassium-depleting diuretics, such as amiloride or triamterene, may also experience this interaction. These diuretics can interact with all absorbable forms of potassium?bicarbonate, citrate, acetate, gluconite, and iodide salts.(9)Severe hyperkalemia is dangerous, and thus patients who are prescribed spironolactone must undergo an evaluation of serum potassium levels.(9)

5)Clonidine and Propranolol
The combination may produce a mysterious hypertension that is unrelated to the pharmacology of either agent when administered independently.(8)A sudden withdrawal of clonidine from adjunctive therapy with propranolol may cause fatal rebound hypertension.
Clonidine is a central alpha-2 adrenergic agonist that suppresses the sympathetic nervous system from the brain.(10)This activity leads to a decrease in the norepinephrine amounts available in the synaptic cleft of the adrenergic neuron. Alpha-1 receptors then become sensitized because of less norepinephrine available in the cleft.(10)When clonidine is suddenly withdrawn, the result is a large increase in norepinephrine in the synaptic cleft of the adrenergic neuron. The sensitized alpha-1 receptors are stimulated, leading to an exaggerated vasoconstriction. The body cannot compensate for this response because the beta-2 receptors are blocked when a patient is concurrently taking propranolol. Within 24 to 72 hours, a dramatic rebound hypertension is noticed.(9)

6)Warfarin and Diflunisal 
Nonsteroidal anti-inflammatory drugs (NSAIDs), such as diflunisal, have been shown to increase the risk for gastrointestinal (GI) bleeding and the anticoagulant response of war-farin.(5)Other NSAIDs?such as keto-profen, piroxicam, sulindac, diclo-fenac, and ketorolac?have been shown to have similar interactions with warfarin. In most patients, however, indomethacin has little effect on hypothrombinemic response.(5)Because the interaction between warfarin and diflunisal can lead to GI bleeding or even fatal hemorrhaging, an alternative to diflunisal is suggested. Acetaminophen is the alternative of choice. Yet, if an NSAID is needed, nonacetylated salicylates?such as magnesium salicylate or salsalate?are safer because of minimal effects on platelets and gastric mucosa.(5)

7)Theophylline and Ciprofloxacin
Concurrent administration may lead to toxic increases in theophylline.(11)This problem occurs because the hepatic metabolism of theophylline is inhibited by ciprofloxacin via the cytochrome P-450 enzyme system. Theophylline is metabolized by CYP1A2 and to a lesser extent by CYP3A4. Ciprofloxacin and other drugs, including clarithromycin, erythromycin, fluvoxamine, and cimetidine, are all potent inhibitors of CYP1A2. Because they have little effect on CYP1A2, levofloxacin or ofloxacin should be considered as an alternative to ciprofloxacin.(5)Theophylline toxicity is a serious condition; several deaths have been linked with serum concentrations as low as 25 mcg/mL.(11)Signs of theophylline toxicity include headache, dizziness, hypotension, hallucinations, tachycardia, and seizures.(11)

8)Pimozide and Ketoconazole
Pimozide alone can prolong the QT interval, and it has been linked with ventricular arrhythmias (torsades de pointes).(5)When pimozide is combined with ketoconazole, the combination can be deadly. Pimozide is a CYP3A4 enzyme substrate, and ketoconazole is a potent inhibitor of CYP3A4. This leads to marked increases in pimozide serum levels.(5)Other drugs?such as itraconazole, clarithromycin, erythromycin, diltiazem, and nefazodone?are also potent inhibitors of CYP3A4 and should not be administered with pimozide.(5)Fluconazole is weaker, but in larger doses it also inhibits CYP3A4. Terbin-afine is a safer choice because it does not affect CYP3A4.(5)

9)Methotrexate and Probenecid
When probenecid is administered with antineoplastic doses of metho-trexate, the result can be a 2- to 3-fold increase in methotrexate levels.(5)Probenecid acts as an active tubular secretion inhibitor and prevents methotrexate from being excreted, thus potentially causing toxicity. The symptoms of severe methotrexate toxicity include diarrhea, vomiting, diaphoresis, and renal failure, and it may result in death.(9,12)This interaction with methotrexate also occurs with penicillins (eg, amoxicillin, carbeni-cillin) and salicylates.(5)The risk with low-dose methotrexate (commonly used for arthritis) is lower; in fact, NSAIDs in combination with low-dose methotrexate are often prescribed purposely.(5)
Possible alternatives include aceta-minophen, as opposed to salicylates or NSAIDs. Celecoxib does not affect methotrexate pharmacokinetics and could be an alternative. However, rofecoxib produces some increases in methotrexate serum concentrations and therefore should be avoided.(5)

10)Bromocriptine and Pseudoephedrine
The interaction can lead to severe peripheral vasoconstriction, ventricular tachycardia, seizures, and possibly death.(5,13)Bromocriptine is an ergot-derived dopamine agonist with several uses, including antiparkinsonian therapy. New treatment guidelines for Parkinson?s disease recommend a first-line therapy change from levodopa to bromocriptine or other dopamine agonists, such as ropinirole, pramipexole, or pergolide.(14)Notable side effects of bromocriptine include thickening of bronchial secretions and nasal congestion.(11)This is significant because it increases the likelihood of a patient taking bromocriptine to self-medicate with an OTC decongestant such as pseudoephedrine. Patients receiving bromocriptine should be advised to avoid all sympathomime-tics.(5) 

Microscopy of some impotant drugs

Microscopy of some impotant drugs

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1-Liquorice- Ulignified Septate fibre
2-Solanacoeus Plants- Anisocytic stomata
3-Rhubarb- Star spots
4-Squill- Ca oxide raphides
5-Cardamom- Clothing of glandular trichome
6-Quillaria- Thin membrane arillus
7-Digitalis- Rhytidomes & Glandular Trichomes
8-Atropa Belladona- Anisocytic Stomata
9-Verbascus Thapsus- Clusters of Ca Oxalate
10-Artemisia- T-Shaped Trichomes
11-Stromanium- Phloem Fibres
12-Nuxvomica – Lignified trichomes
13-Fennel- Reticulate lignified trichomes
14-Coriander- Wavy sclerenchyma
15-Indian Dill- Lateral ridges with vascular bundle
16-Anise- Branched & unbranched vittae
17-Cinnamon- Absence of cork & cortex
18-Ginger- Non Lignified vessels & starch grains , Endodermis with no starch
19-Collapsed Endodermis
20-Caraway-Collapsed Parenchyma
21-Chenopodium-Epidermis with no trichomes
22-Chirata- Stomata on lower surface only with no trichomes
23-Cinchona - Large sclerenchymatous bast cells with Medullary ray.
24-Cinnamon- Parenchyma cells with starch.
25-Colchicum- Spiral Ducts, Parenchyma with starch
26- Coriander- Prismatic and aggregate crystals of calcium oxalate
27-Saffron- Trichome of stigma
28-Turmeric- Parenchyma with pasty starch
29-Digitalis- Glandular trichomes
30-Euclyptus- Crystal bearing fiber
31-Gentian- Large reticulate ducts
32-Liquorice- Parenchyma with crystals and starch
33-Hycyamus- Endosperm tissue with proteid granules and oil.
34-Ipecac- Parenchyma with raphides
35-Mentha- Trichomes, simple, showing cuticular markings (a medium sized trichome).
36-Pilocarpus- Aggregate crystals of calcium oxalate.
37-Podophyllum- Reticulate ducts and tracheids, Spiral duct, Aggregate crystals of calcium
oxalate, Cork
38-Quassia- Medullary ray with starch, Large porous duct
39-Rheum- Parenchyma with starch, resin and crystals, Reticulate ducts.
40-Senega- Parenchyma with fat, Cork & Porous duct.
41-Senna- Bast of vascular bundles, Crystal bearing fibers from vascular tissue
42-Stromanium- Parenchyma cells of petiole
43-Strophanthus- Endosperm tissue, showing oil and crystals, Outer tissue with granular proteid
matter and starch
44-Tobbaco- Parenchyma (collenchymatous) from midrib,Leaf parenchyma with chlorophyll.
45-Ginger- Parenchyma with starch and one cell with resin
46-Belladona- Tracheids and spiral duct, Leaf parenchyma cells with crystals,Bast Cells, Porous
ducts & Crystal Sand
 

Drugs And Their Analogues

Drugs And Their Analogues

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Drug - analogue

zidovudine -thymidine
Didanosine-deoxyadenosine
Lamivudine-cytosine
Stavudine-thymidine
abacavir-guanosine
Ganciclovir-acyclic analogue of guanosine
zalcitabine-homologue of cytosine
Foscornet-pyrophosphate
Tribavirin-guanosine
Sulphonamide- PABA
mithotrixate & folate = pteridin
Streptomycin = streptidin
Gentamycin = deoxy streptamine
Aztreonam = mono bactam
Cephalosporin = cepham
Merapenam , imipenam = carbapenam
Clavulanic acid = OXAPENAM
Pencillin = penam
Ethacrynic acid = phenoxy acitic acid
Metrindazole = 1,2,4 thiazolidin
amiloride = pyrazin & guanidin
Spiranolactone = thioacetic acid at 6th position
atorvastatins-pyrrole
fluvastatins-indole
cerivastatins-pyridine
rosuvastatins-pyrimidine
fibrates-isobutyric acid derivatives
aziritidine-ezetimibe
pyrazine-acipimox
acetazolamide-1,3,4-thiadiazole
thiazide-1,2,4-thiadiazine
 

Revision Of TABLETS

Revision Of TABLETS

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TABLETS
  • 90% of drugs are in oral dosage form.
  • Tablet is unit dosage form.
  • Liquid dosage forms r given in dose of medication 5-30%.
  • Tablet should have 2-4% of moisture.

Evaluation
  • General appearance
    • Size and shape – compressed tablets shape and dimensions are determined by the tooling during the compression process.
Rem-when compression force is constant, tablet thickness varies with changes in die fill, with particle size distribution, packing of particle mix and tab. Weight.
When die fill is constant, thickness varies with variation in compressive load.
*         Crown thickness of tablet measured by micrometer.
*         Total crown thickness is measured by vernier calliper.
*         Tablet thickness should be controlled with ±5% of std. Value.
*         The more the convex the tablet surface more is the capping problem so one has to use slower tablet machine or one with pre compression capabilities.
*         Unique identification markings-given in Physicians Desk Reference(PDR).
*         Product code is given from National Drug Code (NDC).
*         Mottling-non uniformity of colour over tablet surface.
*         For colour quantification 3 methods-reflectance spectrophotometry, tristimulus colorimetry and micro-reflectance photometry.



  • Hardness and Friability
    • Hardness of tablet directly effects dissolution behaviour.
    • It is the force req. to break the tablet in diametric compression test.
    • Hardness also called crushing strength.
Devices used
*         Monsento tester (stockes tester)-easy to handle.Manually operated,gives strength in kgs.
*         Strong-cobb tester-force applied by hydraulic pressure and later air pressure not manually. It gives value 1.6 times higher than the original strength. it gives strength in kgs.
*         Pfizer tester-same principle as pair of pliers.(kgs)
*         Two testers to eliminate operation variations:-
1.Erweka tester-gives strength in Kgs.
2.Schleuniger tester-operates in horizontal position-gives strength in KGs and Strong Cobb units.
  • Hardness and thickness of tablet is a function of die fill and compression force.
  • At constant compression force, hardness increase with increasing die fill.
  • At constant die fill, hardness increase and thickness decrease when compression force is applied.
  • Roche friabilator machine is used for measuring friability of tablet.
Tablets fall from-6 inch distance
Total Rpms-25
Total revolutions-100
Time-4 minutes
Limits-0.5-1.0% (USP),not more than 1% (IP).
  • Effervescent tablets and chewable tablets show higher friability value than above so stack packaging for them.
  • Vickers test is used to measure the surface hardness.
  • ‘Whiskering’ phenomenon is related with tablets with deeply concave surfaces or punches used were in poor condition and such tablets have higher than normal friability values.
HARDNESS LIMITS
TABLET
HARDNESS LIMIT
SOFT
2 KG
SUSTAINED RELEASE
8 KG
GENERAL
4 KG
HARD
6 KG
EFFERVESCENT
1.3 KG

STANDARD HARDNESS SHOULD BE MIN. 4 KG

  • Webster and Van Abbe tester-indicate edge damage during handling.
  • Weight variation
    • Total tablets taken-10.
    • Limits-Tablets meet USP if not more than 2 tablets are outside the limit and no tablet should differ by more than 2 times the original limit.
    • This test is used if the tablet contains 90-95% API. It is not appropriate for low dose containing tablets.API should be more than 50mg. (i.e-potency). For these content uniformity test is used.
Average wt of tablets(mg)
Max. % diff. allowed
130 or less
10
130-324
7.5
More than 324
5

I.P limits
Average wt of tablets(mg)
Max. % diff. allowed
80 or less
10
80-250
7.5
More than 250
5

CONTENT UNIFORMITY TEST:
  • It should be between 95-105%.
  • Tablet potency for this test should be less than 50mg.
  • For digitoxin it is 90-110%.
  • If  larger wt. Variation ,no good content uniformity.
Test:
Total tablets-30
Total assayed-at least 10
9 of the tablets should contain 85-115% API.10th tablet may contain 75-125% API. Test passed
If above conditions not met other 20 tablets should be assayed, and no one should fall outside 85-115% range.
  • Disintegration

  • Apparatus:-
-6 test tubes
-mesh size:10 mesh i.e 1.7mm(USP),8 mesh i.e 2mm(IP)
-glass tubes are 3 inches long
-beaker contains 1L of water, simulated gastric fluid or simulated intestinal fluid.
-temperature: 37±2 degree Celsius. (Remember with reference to difference with dissolution)
-tablets remain 2.5 cm below surface of liquid on upward movement and vice versa.
-no. of cycles per minute:28-32

                                                          IP LIMITS
Tablet/Capsule
liquid
Disintegration time(min)
Uncoated tablet
water
15 min (USP-30 min)
Sugar coated
water
60 min
Enteric coated
0.1N HCl with phosphate buffer
2 hr in gastric fluid media and 1 hr in intestinal fluid(USP it is reverse)
Film coated
Water or 0.1N HCl
30 min
Vaginal tablets
water
30 min
Soluble, dispersible and effervescent tablets
Water
(19-21 deg. Celcius)
3 min
Hard gelatin capsules
water
15 min
Soft gelatin capsules
water
60 min







  • Dissolution
USP
Apparatus 1-Basket type
  • Mesh screen-10 mesh(USP)
  • -temperature: 37±0.5 degree Celsius.
  • 900 ml flask.
Apparatus 2-paddle type
  • 900 ml. Flask.
  • Contains wire helix to prevent tablet from floating.
Limits(USP)
ü  Not less than 75% should be dissolved in 45 min.
ü  90% of the drug should be dissolved in 30 min.(this is not USP limit, it is industrial limit)
ü  Above both values are Q values.
ü   
Dissolution acceptance criteria(IP)
stage
No. Of dosage units tested
Acceptance criteria
S1
6
No dosage unit is less than Q+5%.
S2
6
Average of 12 dosage units is equal to or not more than Q% and no unit is less than Q-15%.
S3
12
Average of 24 dosage units is equal to greater than Q% and not more than 2 dosage units are less than Q-15% and no dosage unit is less than Q-25%.


  • Tablet compression apparatus
    • Dies define shape and size of tablet.
    • Cam tracks guide the movement of punches.
    • Multi-station presses are called rotary presses.
    • Turrets-the portion of the head that hold the upper and lower punches.
    • Fette machines-they chill the compression components to allow compression of low melting solids such as waxes use (in case of suppositories0.

TOOLING
  • BB tooling-most commonly used.length-5.25 inch,nominal barrel diameter-0.75 inch,1 inch head diameter.
  • B tooling-5.25 inch, nominal barrel diameter-3 9/16 inch,1 inch head diameter.
  • D tooling-used for larger tablets. 5.25 inch, nominal barrel diameter-1 inch,1.25 inch head diameter.
  • Dwell time-time for which tablet remains under compression.
  • Remember-Devices which measure compression force at each compression station.
-Pharmakontroll, Killiani Control System, Thomas Tablet Sentine


  • PROCESSING PROBLEMS IN TABLET
1)       Capping and lamination-capping is partial or complete separation of top or bottom parts of tablet from main body of tablet.Lamination is separation of tablet into 2 0r more distinct layers. It is due to:-
- deformational properties of formulation i;e plastic deformation
-deep concave punches.
- absence of adequate moisture.
-tablet tooling
-incorrect setting of press.
 2) picking and sticking-picking occurs due to engraving and embossing.In  sticking tablet material sticks to die wall.
 3) Mottling-uneven distribution of color on tablet.
4) wt. Variation
5) poor flow-talc or colloidal silica helps in improving the flow.poor flow can result in bridging,arching and rat holling.
6) poor mixing
7)punch variation
8)hardness variation
9)double impression

  • TABLET GRANULATION
    • It improves flow properties of tablet.
    • Shape factor of granule should be 6 just like sphere for good flow.
    • The method used for measurement of surface area solid granules or particles are air permeability method and gas-adsorption method(He gas is used).
    • Dense granules require higher compression force to form cohesive compact and they are less friable.
    • For determining granule density-Mercury displacement method is used. O                                       ther method uses benzene as organic solvent.
    • As granule size increase bulk density decreases.
      As particle becomes more spherical bulk density increases.
    • The strength of tablet is mainly due to surface tension of liquid and capillary forces.
    • For measuring granule strength and friability ASTM(American Society For Testing Materials) specification is taken into account and compression strength are taken into account.
  • TYPES OF GRANULATION
    • Dry granulation
*         Also called compression granulation.
*         Used when drug is sensitive to moisture.
*         Slugs are formed in this.so process also called slugging.
*         Roller compactor instrument is used.Can produce 500 kg of slugs.
*         Main advantage is that no need to use excess lubricants.
  • Wet granulation
*         Granules formed by adhesive forces.
*         Surface tension forces and capillary pressure are initially responsible for wet granulation.
*         Solvents are used considering EPA(Environmental Protection Agency) regulations.

EQUIPMENTS FOR WET GRANULATION
  1. 1.        Littleford Lodige mixer- capable of both wet massing and blending.
*         Time taken-30-60 sec.
*         Horizontal in operation.
*         Temperature rise of 10-15 deg. is expected.
2. Diosna mixer or granulator-contains bowl in vertical position.
*         Total time 11-12 min.
3. Littleford MGT mixer-vertical in operation.
4.Gral mixer-modification of planetary mixer(IMP).

  • Direct compression
*         E:g Nacl,KCl can be directly compressed.
*         Uses directly compressible diluents like spray dried lactose.
*         They have good flow and compressibility.
*         Maximum of 30% of API is used in direct compression tablet.

  • TABLET INGREDIENTS 
    • Diluents:
*         Used to increase bulk of tablet.
*         5-80% can be used.
*         All the sugar containing diluents have tendency to undergo reaction with drugs containing –NH2 group. This is called Maillard reaction which only changes color not content.
STARCH
ü  11-14% moisture present
ü  Dried starch has 2-4% moisture. Their moisture level increase to 6-8% following moisture exposure.
ü  Two types:

Directly compressible starch (Sta-Rx 1500)-used as diluents, binder and disintegrant.
Contains 10% of moisture.
Hydrolysed starch (Emdex, Cellutab: contain 90-92%dextrose and 3-5% maltose)-directly compressible. Used in chewing tablets and have 8-10% of moisture.

LACTOSE
  • Three types of lactose.
  1. 1.        Alfa-lactose monohydrate-crystalline nature, has 5% moisture, poor flow and compressibility and used in wet granulation. It gives Maillard reaction.
  2. 2.        Spray dried lactose-<3% moisture.good flow and compressibility. Used in direct compression.it gives Maillard reaction.(in Maillard reaction furfuraldehyde is formed).
  3. 3.        B-lactose(anhydrous)-hygroscopic. used in direct compression and does not gives Maillard reaction.

DEXTROSE
  • Also called cerelose.
  • Can be used instead of lactose.

MANNITOL
  • Used in chewable tablet due to negative heat of solution.
  • Non-hygroscopic.
  • Non-cariogenic.
  • Used in vitamin formulations.

SORBITOL
  • Optical isomer of mannitol.
  • Hygroscopic.

SUCROSE
  • Available as co-processed form such as SUGARTAB(90-95%sucrose + 7-10% invert sugar), DIPAC(97%sucrose + 3% modified dextrins) and NUTAB(95%sucrose+4%invert sugar+Mg.stearate+corn starch).
  • Used in direct compression.
  • Hygsroscopic

Important point-Kaolin and bentonite,diluents, is not used with cardiac glycoside,synthetic estrogens and alkaloids                           
                                                                MICROCRYSTALLINE CELLULOSE
  • Trade name-AVICEL
  • DIRECTLY COMPRESSIBLE
  • Two grades:-PH101(powder) and PH102(granules)
  • Also act as disintegrating agent.
  • Hygroscopic
  • May delay the release of drug.

DICALCIUM PHOSPHATE
  • Non-hygroscopic(just like mannitol)
  • Moisture sensitive drugs can be used with it
  • Not used with tetracycline due to complex formation.

Classification in other way

Wet granulating diluents-alfa lactose,kaolin,bentonite, dicalcium sulphate
Direct compression-spray dried lactose,colloidal silica,NaCl and NaHCO3 for dental cones, direct com. starch.

Binders and adhesives
  • Used to provide cohesive qualities.
  • More the binder, harder is the tablet.

NATURAL GUM

  • Acacia and tragacanth are examples
  • Used in 10-25%

GELATIN
  • Natural protein
  • 10-20% in solution form.
  • Upon storage disintegration time will increase with the use of such binders
Starch
  • 10-20%solution.
  • Give translucent paste.
  • It undergoes hydrolysis to dextrin and glucose.
  • Liquid glucose is 50%solution in water.
Modified natural polymers
  •  Methylcellulose(alcohol soluble, more soluble in cold water than hot water)
  • Hydroxy propylcellulose(alcohol sol.)
  • Hydroxy propyl methylcellulose(water soluble)
  • Ethylcellulose(alcohol soluble,retard D.T)
  • PVP(polyvinyl pyrrolidone) used in 2%.used in aqueous and alcoholic solution.
  • IPA(isopropyl alcohol)-widely used binder.

  • Another classification
ü  solution binders-strach,sucrose,gelatine,acacia,tragacanth.
ü  Dry binders-HPMC.Cross linked PVP.

  • LUBRICANTS
ü  Decrease friction between diewall and tablet surface
ü  Can be used intragranularly(PEG,Vegetable oils) and extragranularly(talc,stearates).
ü  They are hydrophobic in nature.
ü  Fluid lubricant-liq. Paraffin
ü  Boundary lubricant-stearic acid
ü   
  • What is bolting of lubricant?
Lubricant is passed through 60-100 mesh nylon cloth in order to get fine particles this is called bolting of lubricant.

ü  Hydrocarbon/mineral oil
  • Applied as fine spray.
  • Mostly used for aspirin tablets
ü  Calcium and Mg. Stearate
  • used in 1%
  • may cause delay release

ü  Mg.stearate is used with SLS due to its hydrophobic property.
ü  It is not used with acidic drugs

                     
  • Compritol 888
ü  It is glyceryl monoester of behenic acid.

  • Water soluble lubricants
ü  Sodium enzoate,sodium acetate,NaCl,leucine,PEG etc.

  • GLIDANTS
1)       Talc
  • Used in 5%.
  • Can also be used as anti-adherent.
  • Contains traces of iron so may act as catalyst for the drugs which are degraded by Fe.
  • Also contain calcium so not used with tetracycline.

2)       Colloidal silica
ü  Available in 3 forms
ü  Cab-o-sil(<1%)
ü  Aerosil(0.25-3%)
ü  Syloid.

Corn starch
ü  Use in 5-10%


                                                                                DISINTEGRANTS
  • Facilitate breaking up of tablet
Act by 3 mechanism
  1. 1.        By swelling
Alginate, starch dye, PVP
  1. 2.        By wetting
SLS, Clay, Bentonite

  1. 3.        Effervescent
NaHCO3 and citric acid

Examples
STARCH
ü  5-20%
ü  Modified starches are used which are: Primogel and Explotab. they are low substituted carboxymethyl starches.(1-8% used,but 4%is optimum)

  • Clays
ü  Veegum (Mg. Aluminium silicate)(10%)
ü  bentonite(10%)
  • both are used only for colored tablets
  • they are most effective in sulfathiazole tablets.
    • Super disintegrants
ü  They are used in lower concentration. of 2 % to 6 %,while traditional disintegrants such as starches often require concentrations of about 20 %. 

  
Sodium Starch Glycolate

  
Sodium Carboxymethyl Starch
  
Croscarmellose Sodium

  
Soy Polysaccharides
  • Primojel®, sodium starch glycolate, and Primellose®, croscarmellose sodium, which show outstanding disintegration characteristics for tablets prepared by direct compression, wet granulation and for capsule formulations.  

COLORING AGENTS
ü  Lake are the dyes that have absorbed on hydrous oxide
ü  As coloring concentration increases, mottling increases.
ü  To improve photosensitivity of dye use of UV absorbing chemical such as benzophenone can be used.

v  DI-PACLINE is a commercially available directly compressible sugar.

SWEETENERS
ü  Used in (0.5-0.75%)
ü  Cyclamates can be used.they are 70 times more sweeter than sugar. But are carcinogenic
ü  Aspartate(phenyl ester of methylacetic acid).180-200 times sweeter than sugar and non-carcinogenic.
ü  Saccharin is carcinogenic and 500 times more sweeter than sugar.
ü  Mannitol is used in chewable tablets and 72 times more sweeter than sugar.

SOME INSTRUMENTS
MIXING
ü  For large qt. Of powder-twin-shell blender,double-cone blender,planetary mixer.
ü  For continuous production-ribbon blender,roto cabe-blender
ü  Mass mixer-sigma blade mixer
ü  High speed granulators-Diosna mixer,Littleford MGT,Gral mixer

ü  For continuous production extruders are used E:g Reitz extruders
ü  Topo granulators-to prepare granules under high vaccum.

ü  Spheronization-refers to formation of spherical particle from wet granulation.
ü  Marumerizer and CF-granlator are used for spherozination

  • Spray congealing/spray chilling
ü  It is the process consist of melting solid and reducing them to beads or powders by spraying molten feed into stream of colder air or gases.

ü  Monoglycerides are spray congealed at 50 deg F
ü  Carbohydrates are sparay congealed at 167 deg F

  • Important information
ü  Versa press is used for the the preparation of layered tablets.
ü  Manestey dry cota instrument is used.implantation tablets should have size of less than 8mm.
ü  Kern-injector-contain hollow needle and plunger. used for administration of rod shaped tablet.
ü  For sub-lingual and vaginl tablets, lactose is used as diluent.

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