M.Phil Pharmaceutical Chemistry

Institute Of Pharmaceutical Sciences (IPS)

UVAS Lahore

Background:M.Phil Pharmaceutical Chemistry is a research based degree in Pharmacy Profession. Human resource with this qualification is of high demand in pharmaceutical market including; Academia, Pharmaceutical industry and R&D departments.

Only few universities are offering this degree in Pakistan. So, the pharmaceutical market is facing shortage of Pharmacist with M.Phil degree in pharmaceutical chemistry.

UVAS can use its strengths to take benefit out of these crises and fulfill this vacuum to satisfy the market demand by initiating this research based degree of M.Phil Pharmaceutical Chemistry.

Strengths:

1. UVAS is a research oriented university2. Different departments of university as already engaged in active research and university has

experience of running research based programs.3. Research facilities in the form of equipment similar to the required for research in

pharmaceutical chemistry are available in university and also in IPS.4. Adopting HEC approved curriculum designed by experts of this field.5. IPS already has many facilities (Particularly Subject experts) needed for research in this

program.

Opportunities:

1. To be in the list of few institutions awarding this degree.2. Number of research publications and university ranking will improve.3. Our students can fulfill the existing vacuum in the market demand and supply of

Pharmaceutical chemists.4. IPS graduates interested in M-Phil Pharmaceutical Chemistry can enroll themselves in this

program

Eligibility criteria:

Pharm-D (Doctor of Pharmacy) Valid NTS GAT ( General)

M.Phil Pharmaceutical Chemistry

Course Outline (As Per HEC)Sr.No. Course No. Course Name Credit Hours

1- PCHM1001 Analytical Chemistry-I 3(2-1)

2- PCHM1002 Drug Design & Synthesis 2(1-1)

3- PCHM1003 Combinatorial Chemistry 2(2-0)

4- PCHM1004 Drug Stability & Drug Group Analysis 3(2-1)

5- PCHM1005 Analytical Chemistry-II 3(2-1)

6- PCHM1006 Isolation & Separation Techniques 2(1-1)

7- PCHM1007 Polymers in Controlled Drug Delivery System 3(2-1)

8- Biostatistics 3(3-0)

M.Phil Pharmaceutical Chemistry

Course Outline Semester System

Semester-ISr.No. Course No. Course Name Credit Hours

1- PCHM1001 Analytical Chemistry-I 3(2-1)

2- PCHM1002 Drug Design & Synthesis 2(1-1)

3- PCHM1003 Combinatorial Chemistry 2(2-0)

4- PCHM1004 Drug Stability & Drug Group Analysis 3(2-1)

Semester-IISr.No. Course No. Course Name Credit Hours5- PCHM1005 Analytical Chemistry-II 3(2-1)

6- PCHM1006 Isolation & Separation Techniques 2(1-1)

7- PCHM1007 Polymers in Controlled Drug Delivery System 3(2-1)

8- Biostatistics 3(3-0)

Semester-III & IVSr.No. Course No. Course Name Credit Hours9- PCHM1020 Research work &Thesis submission 20(20-0)

PCHM1001: Analytical Chemistry-I ( Electro analytical Techniques) : 3(2-1)

A-Introduction to Electrochemical methods:

Classification of electrochemical methods, advantages and limitations of electrochemical

Methods, electrochemical terminology, Principles of electrochemical cell, Nernst equation, potential generation across membrane, ion-selective electrodes, dropping mercury electrode, rotating platinum, gold and carbon electrodes.

B-Controlled-Potential Techniques:

Chronoamperometry, Chronocoulometry, D.C. polarography, cyclicvoltametry, Rotating disc voltametry, Amperometric titrations.

C-Controlled-Current Techniques:

Chronopotentiometry, Cyclicchronopotentiometry, Electrochemical sensors, Photo electrochemistry, electrochemical analysis of substances of pharmaceutical and biological interest, electrochemical study of the mechanism of organic reactions.

Practicals:At least ten practical will be conducted for this course.1-Conductimetric titration of metallic ions (NaCl)2- Water analysis.3- Conductivity of different types of water.4-Potentiometric titration of weak acids and bases.5- Potentiometric titration of different oxidizing and reducing substances.6-Calibration of pH meter.7-To find out the Relationship between milli volts (mV) and pH meter.8-Analysis of commercial product of different ions.9-Estimation of Hydroxyl groups in Phenols.10-Determination of number of Carboxyl groups in different drugs.Recommended Books:1. P T Kissinger and W R Heinemann. Laboratory Techniques in Electro analytical Chemistry. Marcel Dekker, New York, 1984.2. A J Bard and L R Faulkner, Electro-chemical Methods: Fundamentals and Applications. Wiley, New York, 1980.3. A M Bond. Modern Polarographic Methods in Analytical Chemistry. Marcel

Dekker, New York, 1980.4. Y YGurevich, Y V Pleskor and Z A Rotenberg, Photo electrochemistry. Plenum

Press, New York, 1978.5. J Fitzgerald, Ed., Analytical Photochemistry and Photo chemical Analysis. Marcel

Dekker, New York, 1971, Chapter 7.6. RN Adams. Electrochemistry at Solid Electrodes, Marcel Dekker, New York, 1980.

PCHM 1002: Drug Design & Synthesis: 2(1-1)

A-Drug Designing and Synthesis:

Drug design, concept, target oriented drug design, and pharmacokinetic drug design. Stereo-chemistry of drug molecules and their Pharmacologic activity. Study of drug receptor interaction with special reference to the mechanism of action of drug molecule. Some stereo chemical properties of possible receptor, with particular reference to morphine related compounds. Synthesis of compounds in accordance with molecular structure activity relationship. Structure activity relationship determined by direct bonding studies.

B-Quantitative model construction:

Property based models, structure based model, properties calculated by MO theory, molecular confirmations. Computer graphic simulations. Rational drug design. Principles of molecular graphics. Principles of computational chemistry of drug.

C. Macromolecular Targets for Drug ActionConcepts of bio-selectivity in drug. Structure and properties of macromolecules.Enzymes and receptors. Molecular targets for design and development of drug.Lead compounds, basic concept and its natural and synthetic sources.Intercalation of drugs, mono functional intercaltors, antitumor, antibiotics,Synthetic anti-tumor agents, acridines and anthraquinones. Polyfunctional quinozaline diacridines bisanthracycline, 4-flouroquinolones.Peptidoglycanes, main structure, cell wall model, β-lactam antibiotics.Therapeutic effects of the inhibition of sterol metabolism with specific referenceto hypo-cholesterolemic drugs.Practicals:At least ten practical will be conducted for this course.1-Synthesis of Aspirin2- Synthesis of Ascorbic Acid.3-Preparation of Methyl salicylate4-Synthesis of Benzocaine5-Preparation of acetaminophen6-Preparation of Iodoform7- Preparation of Ammonium Chloride8- Preparation of Potash Alum9-Study of different designs adopted for the preparation of various drugs10-Assignment for the preparation of new drugs

Recommended Books:1. J Perun and C L Propst, Computer-Aided Drug Design Methods and Applications.

Marcel Dekker Inc, New York, 1989.2. Y C Mastin, Quantitative Drug Design. Vol. 8, Marcel Dekker Inc, New York 1978.3. B Testa, Ed., Advances in Drug Research. Vol. 18-20, Academic Press, New York,

1990-91.4. B Stenlak, Foundation of Molecular Pharmacology. Medicinal and

Pharmaceutical Chemistry. J Athline Press, London, 1979.5. J B Stenlake. Foundation of Molecular Pharmacology. The Chemical Basis of

Drug Action. Athlone Press, London, 1979.6. Forman J C and Johanson T, Textbook of Receptor Pharmacology. CRC Press, Boca Raton, Fl. USA, 1996.7. E, Mustschler and E, Winterfeld. Trends in Medicinal Chemistry.VGH Germany,

1986.8. B Testa, Advances in Drug Research. Academic Press, New York, 1990.9. Roberts S M and Prince B J, Ed. Medicinal Chemistry. The Role of Organic

Chemistry in Drug Research. Academic Press, 1985.10. C Hansch, Comprehensive medicinal Chemistry. Vol 1 to 6, Pergaon

PCHM1003: Combinatorial Chemistry: 2(2-0)

Introduction to reactive and functional polymers. Functional bead shaped materials, synthesis and characterization. Polymer – supported reactions versus solution-phase reactions. Automated synthesis the breakthrough point. Synthesis of polypeptides, polynucleotide.

Combinatorial chemistry-principles. Combinatorial chemistry-methods. Combinatorial chemistry drug design and combinatorial methodology. Design of new materials by combinatorial chemistry. Design of new catalysts by combinatorial chemistry. Possible limitations of combinatorial chemistry .Redesigning combinatorial technology-from here to the unknown.Recommended Books:1. Delgado J M and Remers, W A Gisvolds. Textbook of Pharmaceutical and Medical

chemistry. J B Lippincott Co, 9th Ed., 1991.2. Wolff M E Burgers Medicinal Chemistry, Wiley Inter science, 4th Ed.1981 Ed. Vols

1–111.3. Diversity. Michael R Pavia, The Chemical Generation of Molecular. Sphinx

Pharmaceuticals. A Division of Eli Lilly, 1995.4. Adnan M M Majalli and Barry E Toyonaga, Solid Support Combinatorial

Chemistry in Lead Discovery and SAR optimization, Ontogen Corporation, 1995.5. Sarvajit Chakravarty, Babu J Mavunkel, Robin andy, Donald J Kyle, Non-peptide

Bradykinin Receptor Antagonists From a Structurally Directed Non-Peptide Library.Scios Nova Inc, 1995.

6. Keith Davies and Clive Briant, Combinatorial Chemistry Library Design using Pharmacophore Diversity Chemical Design Ltd.1995.

7. Craig James and David Weininger, A Database System for Combinatorial Synthesis Experiments. Daylight Chemical Information Systems Inc, 1995.

8. Keith Davies and Catherine White, An Information Management Architecture for Combinatorial Chemistry, Chemical Design Ltd, 1995.

9. R S Pearlman, Laboratory for Molecular Graphics and Theoretical Modeling, Novel Software Tools for Addressing Chemical Diversity. College of Pharmacy,University of Texas, 1996.

10. Yvonne Connolly Martin, Opportunities for Computational Chemists Afforded by the New Strategies in Drug Discovery: An Opinion. Computer Assisted Molecular Design Project, Abbot Laboratories, 1996.

11. Arno F Spatola, Combinatorial Chemistry and Molecular Diversity Course at the University of Louisville: A Description. Department of Chemistry, University of Louisville. 1996.

12. Michael R Pavia, Chemically Generated Screening Libraries: Present and Future. Sphinx Pharmaceuticals. A Division of Eli Lilly, 1996.

13. Michael J Sofia, Chemical Strategies for Introducing Carbohydrate Molecular Diversity in to the Drug Discovery Process. Trans cell Technologies Inc, 1996.

14. Maryjo Zaborowski, Chiron Corporation and Sheila H DeWitt. Data Management for Combinatorial Chemistry. Parke-Davis Pharmaceutical Research, Division ofWarner-Lambert Company, 1995.

PCHM1004: Drug Stability & Drug Group Analysis: 3(2-1)

A-Drug Stability and Drug Group Analysis:Drug decomposition, stabilization and preservation, Kinetics of complex reactions, accelerated

storages tests, expiry dates.

B-Effect of physical and chemical factors on drug stability:Thermal and photo stability of pharmaceutical substances in solid and liquid dosage forms; photo

chemical interaction, photo catalysis and photosensitization of drugs.Oxidative,hydrolytic

addition, racemization and epimerization reactions using drug as typical examples. Application

of various analytical methods to the assay of antibiotics, benzodiazepines, phenolthiazines,

Steroids and sulphonamides

Practical:At least ten practical will be conducted for this course.

1-stability of different drugs susceptible to environmental conditions

2- Stability of Ranitidine HCl.

3- Stability of Vitamin C products

4- Stability of Acetyl salicylic Acid

5- Stability of NaOH and finding out the titer of 1 N solution.

6-Accelerated stability studies of different products available in market.

7-Preparation of a product and observation of different physical and chemical aspects in different

environmental conditions (continued).

8-Continuation of stability studies (physical and chemical testing)

9- Continuation of stability studies (physical and chemical testing).

10-Compilation of Data and finding out results.

Recommended Books:

1. C A Connors, G L Amidon and J J Stella, Chemicals Stability of Pharmaceuticals. Willey-Inter science, New York, 1986.

2. 22. I Lachman, H A Lieberman and J L Kanig. The Theory and Practice ofIndustrial Pharmacy.3rd Eds. Lea and Febiger, Philadelphia, 1986, Chapters 26-28.

3. 23. M S Cooper, Ed. Pharmaceutical Product Stability in: Quality Control in the Pharmaceutical Industry. Vol. 2, Academic Press, New York, 1973, pp141 238.

4. 24. J T Carstensen, Theory of Pharmaceutical System. Vol. 1, chapter 4; Vol 2. Academic Press, New York, 1973.

5. 23. I H Stockely, Drug Interaction. 2nd Ed., Black Well, Scientific Publication, London, 1991.

PCHM1005: Analytical Chemistry-II ( Spectrophotometric Analysis): 3(2-1)

A-Instrumentation:

Radiation sources, mono cheromators, detectors, signal processors, read-out devices, single and double beam spectrophotometers.

B-Ultraviolet and Visible Spectrophotometery:

Origin of molecular spectra, electronic transitions, solvent and steric effects, charge transfer spectra. Analysis of multi component systems, irrelevant absorption corrections.

C-Difference, derivative and dual-wavelength Spectrophotometery:

Application in determination of molecular weight, rate constants and ionization constants;

Spectrophotometric titrations.

D-Infrared spectrophotometery:

Near infrared spectroscopy, Fourier transforms infrared spectroscopy, quantitative analysis.

E-Fluorescence Spectrophotometery:

Factors affecting fluorescence, quantitative analysis of single and two component system, derivatization reactions, advantages of flourimetric methods.

F-Transient Absorption Spectroscopy:

Flash spectroscopy, transient absorption spectra and life-time measurements of singlet, triplet and radical species.

G-Analytical Development in Spectrophotometery:

Physical and chemical properties of medicinal and Pharmaceutical substances relevant to analytical development: colorimetric, enzymatic and photochemical reactions in spectrophoto metric analysis, analytical problems in Multi component systems and formulated products, development of stability Indicating assays.

Practical:

At least ten practical will be conducted for this course.

1-Detailed study and handling techniques of UV-Visible spectroscopy

2-Calibration of UV-Visible Spectrophotometer

3- Quality control analysis of Diclofenac Sodium.

4-Testing of different dosage form in reference to the UV-Visible spectroscopy and Infra red

spectroscopy.

5- Identification of Known compound using FTIR.

6- Study of different brands of Drugs available in Market on spectrophotometer.

7- Comparison of the results and conclusion of data.

8- Formation of calibration curve and concentration of an unknown concentration.

9-practical assignment

10-Project

Recommended Books:

1. D A Skoog and D M, West Principles of Instrumental Analysis. 2nd Wed., Holt-Saunders, Philadelphia, 1980, Chapters 18-22.

2. H H Bauer, G D Christian, JEO Reilly, Allyn and Bacon. Instrumental Analysis. Boston, 1978, Chapters 1-5.

3. D J Pasto and C R Johnson. Organic Structure Determination. Prentice Hall, Inc, Englewood Cliffs, NJ, 1969.

4. Mc Lafferty W A, Interpretation of Mass Spectra. 2nd Ed., F W Benjamin, Inc,Philipsines, 1973.

5. R C Crippen. Identification of Organic Compounds with the Aid of GasChromatography. McGraw-Hill, Inc, New York, 1973.

6. C S Creaser and AMC Davies, Analytical Applications of Spectroscopy. Eds., Royal society of Chemistry, London, 1990,

7. K Florey, Ed. Analytical Profiles of Drug Substances. Vol 1-20, Academic Press, New York, 1972-1991.

PCHM1006: Isolation& Separation Techniques: 2(1-1)

A-General Principles: Extraction methodology.B-Chromatography: Definition and basic principles of chromatographic procedure.Adsorption Column Chromatography:Theory, stationary and mobile phase chromatography, application to the analysis of drugs and metabolites.Paper Chromatography:Ascending and descending techniques, solvent systems, visualization. Open-Bed Chromatography.Thin-layer chromatography:Theory, types of stationary phases and solvents, visualization and identification qualitative and quantitative applications to the analysis of drugs and metabolite.Adsorption Column Chromatography:Theory, stationary and mobile phase chromatography, application to the analysis of drugs and metabolites.High Performance Liquid Chromatography:Theory, stationary and mobile phase, recent advances, applications to the analysis of drugs and metabolites.Gas Chromatography:Theory, retention properties of stationary phases, derivatization techniques (methylation, acylation, silylation, etc) capillary GC, GC-Mass spectrometry application to the analysis of drugs and metabolitesSize Exclusion Chromatography:Theory, types of stationary phase, separation of high molecular weight organic compounds and biopolymers.Practical:Extraction and isolation of various crude drugs.

At least ten practical will be conducted for this course.

1-Extraction of Rauwolfia serpentina by Soxhelt method using solvents of various polarities.

2-Isolation of phytochemicals from Rauwolfia serpentina extract by TLC

3- Isolation of phytochemicals from Rauwolfia serpentina extract by column chromatography.

4- Detection of different components by using different techniques.

5- Extraction of Colchicum autumnale by Soxhelt method using solvents of various polarities

6- Isolation of phyto chemicals from Colchicum autumnale by TLC

7- - Isolation of phytochemicals from Rauwolfia serpentina extract by column chromatography.

8- Detection of different components by using different techniques.

9- Extraction of Glychrrihza glabra by Soxhelt method using solvents of various polarities

10-Isolation of phyto chemicals from Glychrrihza glabra by TLC and column chromatography.

11-- Detection of different components by using different techniques.

Recommended Books:

1. C F Simpson, Practical High-Performance Liquid Chromatography, Heydon and Sons London, 1997.

2. J N Done, I H Konox and J Lohear, Application of High Speed LiquidChromatography, Willey New York, 1974.

3. R L Grob, Ed. Modern Practice of Gas Chromatography, Wiley-Inter science, New York 1977.

4. J Q Walker M T Jakson, Jr and J B Maynard Chromatographic System. 2nd Ed., Academic Press, New York, 1977.5. E Haftmann. Chromatography. 3rd Ed., Van Nostsrand Rehinhold, New York, 1975.6. J M Miller, Separation Method in Chemical Analysis. Willey, New York, 1975.

PCHM1007: Polymers in Controlled Drug Delivery System 3(2-1)

A- Introduction to synthetic polymers.

B-Conventional Vs. controlled release:

Advantages and disadvantages, Pharmacokinetic consideration, Polymer as drug carrier.

C-Monolithic matrix controlled systems:

Dissolved drugs, Dispersed drugs, Drug dissolution/diffusion controlled system.

D-Member controlled system:

Constant activity reservoir, unsteady state analysis (time-lag and burst effect), Drug release from multilayer membrane devices, Drug release from membrane matrix system.

E- Swelling controlled systems:

Hydro gels, Polymer degradation and erosion, Erosion/drug diffusion controlled, Swelling/erosion controlled.

Practical:At least ten practical will be conducted for this course.

1-Extraction techniques for different polymers. (Acacia, tragacanth, polycarbopols, Tween20,

Tween80, spans 20, 80)

2-Preparation of different gels by using different polymers.

3- Matrix and microencapsulation of poorly soluble drugs.

4- Preparation of microcapsules by phase separation method.

5-Preparation of microcapsules by solvent evaporation method.

6- Preparation of oral hydrogels and stability testing.

7- Preparation of trans dermal hydro gels

8- Preparation of floating matrix tablet by using synthetic polymers

9- Preparation of trans dermal patch by using polymers.

10- Synthesis of synthetic polymers by applying different reaction conditions

Recommended Books:

1. Lee and Robinson, Controlled Drug delivery: Fundamentals and Applications. Marcel Dekker Inc, New York, I Lachman, H A Lieberman and J L Kanig. The Theory and Practice of

2. Industrial Pharmacy. 3rd Eds. Lea and Febiger, Philadelphia, 1986, Chapters 26-28.

8-Biostatistics 3(3-0)

A-Introduction: What is Biostatistics? Application of statistics in biological and pharmaceutical sciences.B-Sample and Population: Simple random sampling, Sampling distribution and standard error, Stratified random sampling, Systemic and cluster sampling.C-Test of Hypothesis and significance:Statistical hypothesis, Level of significance, Test of significance, Confidence intervals, Test involving binomial and normal distribution.D-Goodness of fit test: Chi-square distribution, it properties and application, Contingency tables, Test of homogeneity.E-Student "t" and "F" Distribution: Properties of "t" distribution and "F" distribution, Test of significance based on "t"-distribution and "F"-distribution.F-Analysis of variance:One-way classification, Partitioning of sum of squares and degree of freedom, Two-way classification, multiple compression tests such as LSD, P-values, and the analysis of variance models.G-Experimental Designs: (Advantages & Disadvantages):Basic principles of experimental designs, the completely randomized designs (CR-designs), and Randomized complete block designs (RCB designs), Latin square designs (LS-designs), Factorial experimental designs, Computer methods of statistical evaluation, Correlation/regression analysis.

Recommended Books:

1. Nilton, J S and Tsokos, J D Statistical Methods in Biological and Health Sciences. McGraw-Hill, 1983.

2. Sher Muhammad Chaudhry Part-I and Part-II, Introduction to Statistical theory. Ilmi Kitab Khana, Urdu Bazaar, Lahore.

3. Remington R D, Schork M A Statistics with Application to the Biological and Health Sciences. Prentice Hall Inc, New Jersey, 1985.

4. Schefler W C, Statistics for Biological Sciences. Addison Wesley Pub Co. Sydney, 1979.

5. Wardlow A C, Practical Statistics for Experimental Biologists. John Wiley and Sons, New York, 1985.

6. Danniel WJW, Biostatistics, A Foundation Analysis in the Health4th Ed., Wiley Series, New York, 1987.