PHARMACEUTICAL ANALYTICAL TECHNIQUES

UV-Visible Spectroscopy: Basic principles, interaction of electromagnetic radiation with matter and its effects (electronic transitions). Concept of chromophore and auxochrome, effect of conjugation, solvent and pH. Instrumentation (components and their significance). Absorption spectra of organic compounds and complexes illustrating the phenomenon and its utilization in qualitative and quantitative studies of drugs including multicomponent analysis. Woodward-Fieser rules for calculating absorption maximum for unsaturated hydrocarbons. Difference and derivative spectra.

Infra-Red Spectroscopy: Interaction of infrared radiation with organic molecules and it’s effects on bonds. Instrumentation- Dispersive IR spectrophotometers and Fourier transform spectrophotometers. Sample handling for IR spectroscopy. Interpretation of IR spectra.  Brief note on ATR. (Attenuated Total Reflectance).

Nuclear Magnetic Resonance Spectroscopy: Fundamental principles of NMR,  instrumentation (components and their significance). Chemical shifts concept, spin- spin coupling, spin-spin decoupling, shielding and deshielding, solvents. signal multiplicity phenomena in high resolution PMR. Interpretation of PMR spectra.

Brief introduction about Carbon-13 NMR and 2D NMR Spectroscopy.

Mass Spectrometry: Basic principles and instrumentation (components and their significance). Ionization techniques, mass spectrum and its characteristics, molecular ion, metastable ions, fragment ions; fragmentation processes, fragmentation patterns and fragment characteristics in relation to parent structure and functional groups. Relative abundances of isotopes and their contribution to characteristic peaks.

Chromatographic Techniques: Classification of chromatographic methods based on mechanism of separation and their basic principles. Gas chromatography: Instrumentation, column efficiency parameters, derivatisation methods, applications in pharmaceutical analysis. Liquid chromatography: Comparison of GC and HPLC, instrumentation in HPLC, normal and reversed phase packing materials, column selection, mobile phase selection, efficiency parameters, applications in pharmaceutical analysis. Instrumentation and applications of HPTLC, ion exchange chromatography, gel permeation chromatography, chiral chromatography, flash chromatography, and supercritical fluid chromatography (SFC).

Electrophoresis: Principles, instrumentation and applications of moving boundary electrophoresis, zone electrophoresis (ZE), isotachphoresis, isoelectric focusing (IEF), continuous electrophoresis (preparative) and capillary electrophoresis. SDS gel electrophoresis and blotting techniques.  

Radio immunoassay and ELISA: Principle, instrumentation, applications and limitations. 

DRUG DESIGN AND MOLECULAR PHARMACOLOGY

Pharmacokinetics approach to New Drug Discovery

Basic concepts and Defination, importance of ADME parameters in disposition, therapeutics and development their implication on drug discovery.

Overview on computer aided Drug design (CADD) including QSAR, Combinational                  Chemistry, High Throughout screening (RTS)

Molecular Basis of Drugs Action: Cell signaling, communication between cells and their environment, ion-channels, organizations of signal transduction pathways, third messengers, biosensors.

Drug Latentiation :Basic concept,  Prodrugs of functional groups, Bio-precurssor prodrugs, chemical delivery system. 

Biotechnology in Drug Discovery: Cloning of DNA, Expression of cloned DNA, Manipulation of DNA sequence information, New Biological Targets for Drug Development Novel Drug Screening strategies, Novel Biological Agents, Antibodies, Antisense eligonucleotide therapy, Gene therapy.

Herbal Neutracauticals as new source for medicines.

Study of Advanced drugs from natural sources of following groups:

Anticancer, Anti AIDS, Hepatoprotectives, Antidiabetics, Brain Toni cs, Anti urolithiates, Antifilarial, Antihyperlipidimics.

Modern  phytochemical screening techniques and evaluation of herbal drugs and

 their extracts and  formulations, Concept of Reverse Pharmacognosy.

BIOASSAYS AND SCREENING METHODS

Drug discovery process:  Principles techniques and statergies used in new drug discovery.  High throughout screening. Human genomies robotics and economics of drug discovery, Regulations, for laboratory animal care and ethical requirements. 

 Bioassays : Basic principles of bioassays  official bioassays, experimental models and statistical designs employed in biological standardization. Biological  standardization of vaccines and sera with certain examples with reference to IP. Development of new bio assay methods.

 Preclinical  models employed in the screening of new drugs belonging to following categories.

Antifertility agents, sympathomimetics, parasympathomimetics, muscle relaxants (both central and peripheral). Sedatives, hypnotics, antiarrhythmic agents, cardiac stimulants, cardiotonic agents bronohodilators, antihistaminics, eicosanoids.

  Antipsychotic agents, antianxiety agents nootropic drugs antidepressant drugs; antiparkinsonism agents, anticpileptics; analgesics and anti-inflammatory agents; antiulcer agents; infarction; antiatherosclerotic drugs; antidiabetics; models for status epilepticus drugs. cerebroventricular and other newer techniques of drug administration and development; transgenic animals and other genetically prone animal models.

 Alternatives to animal screening procedures, cell-line handling and maintenance and propagation of cell lines, patch-clamp technique, in-vitro cell line based assays diabetics and arthraitis models, molecular biology techniques.

 Principles of toxicity evaluations, ED50, LD50 and TD values, International guidelines (ICH Ethics and animal experimentation recommendations).Guidelines and regulatory agencies – CPCSEA,OECD,FDA, FHSA,EPA,EEC,WHO etc,

 Introduction to biostatistics, parametric and non-parametric tests.  Regression and correlation: Linear regressions, Method of least squares; correlation coefficients, rank correlation, multiple regression Tests of significance: testing hypotheses, tests of significance based on normal distribution. t-test; significance of correlation coefficient. F-test and Analysis of Variance: 1-Way, 2-Way and 3-way classification, Chi-square test of (i) Variance of a normal population (ii) Goodness of fit, (iii) Independence in contingency tables. Non parametric tests, order statistics, sign test, run test, Median test.

BASIC PRINCIPLES OF TOXICOLOGY 

 

 General principal of regulatory toxicology. Use of animals in preclinical toxicology studies, role of preclinical toxicology in drug discovery and development process. Experimental considerations for assessing possible human risk. Flow chart for development of preclinical testing. Dose conversion factors, clinical signs toxicity.    

Single dose and repeat dose toxicity studies; Factors influencing such studies such as species, sex, size, route ,dose level; Data evaluation and regulatory requirements. Determination of Maximum Tolerated Dose (MTD) and LD 50 as per revised OECD guidelines. Allergenicity testing, dermal toxicity, immunotoxicology and in vitro methods of toxicology.  

         Reproductive toxicology assessment of male reproductive toxicity, spermatogenesis; Risk assessment in male reproductive toxicity; Female reproductive toxicology; Oocyte toxicity; alterations in reproductive endocrinology; Relationship between maternal and developmental toxicity.

Mutagenicity; Mechanisms of mutagenesis, point mutations,; Individual chromosomes and complete genome mutations, germ cell mutations, somatic cell mutation; Tests systems in vitro, chromosome damage and chromosomal aberration test, gene mutation, in vivo micronucleus tests in rodents, metaphase analysis.     

Preclinical toxicological requirements for biologicals and biotechnological products; safety analysis; problems specific to recombinant products, toxicokinetics, principles of GLP as per OECD guidelines for conducting preclinical toxicity studies

ADVANCES IN PHARMACOLOGY

Receptor Pharmacology

                  General aspects of receptor pharmacology,structural and functional aspects of receptor s, regulation of receptors,isolation,classification and characterization of receptors.

 

Neurotransmission Pharmacology

                  General aspects and steps involoved in neurotransmission

                  Neurohumoral transimission in autonomic nervous system.

                  Neurohumoral transmission in central nervous system

                  Non-adrenergic non-cholinergic transmission [NANC].

A detailed study of the mechanism of  action, pharmacology of drugs used in 

ANS-Parasympathomimetics and lytics, sympathomimetics and lytics, agents acting at neuromuscular junction and ganglia. 

CNS- General anaesthetics, sedatives, hypnotics. Drugs used to treat anxiety, depression, psychosis, mania,epilepsy, neurodegenerative deseases, drug dependence and addiction.

CVS- diuretics, anti ischemics, antihypertensives, antiarrythmics, drugs for heart failure and dyslipieiemia.

  

A detailed study of the mechanism of action, pharmacology of drugs used in

                   Autocoid pharmacology- a study of the mechanisms involved in the

                   formation, release, pharmacological actions and possible physiological role                    

                   of histamine,serotinine,kinins,prostaglandins,opioidautocoids and cyclic

                   3’ – 5’ AMP. Systemic pharmacology of drugs acting as agonists and antagonists

                   to the autocoids.

                   GIT Pharmacology – anti ulcer,prokinetics,antiemetics, antidiarrhoeal and drugs for

                   constipation and irritable bowel syndrome.

Hormone and hormone antagonists.Anti biotics and chemotherapeutic agents.Analgesics and anti-inflammatory agents.   

                                                          

                FREE RADICAL AND IMMUNO PHARMACOLOGY

                      

   Generation of free radicals, role of free radicals in etiopathology of various diseases, protective activity of certain important antioxidants. Cell and biochemical mediators involved in allergy, immunomodulation and inflammation. Classification of hypersensitivity reactions and diseases involved. Therapeutic agents for allergy, asthma, COPD and other immunological diseases with emphasis on immunomodulators.