Advanced Biopharmaceutics and Pharmacokinetics

Unit 1

Drug Absorption from the Gastrointestinal Tract:
Gastrointestinal tract, Mechanism of drug absorption, Factors affecting drug absorption, pH–partition theory of drug absorption. Formuulation and physicochemical factors: Dissolution rate, Dissolution process, Noyes–Whitney equation and drug dissolution, Factors affecting the dissolution rate. Gastrointestinal absorption: role of the dosage form: Solution (elixir, syrup and solution) as a dosage form ,Suspension as a dosage form, Capsule as a dosage form, Tablet as a dosage form ,Dissolution methods ,Formulation and processing factors, Correlation of in
vivo data with in vitro dissolution data.Transport model: Permeability-Solubility-Charge State and the pH Partition
Hypothesis, Properties of the Gastrointestinal Tract (GIT), pH Microclimate Intracellular pH Environment, Tight-Junction Complex.

Unit 2

Biopharmaceutic considerations in drug product design and In Vitro Drug Product Performance: Introduction, biopharmaceutic factors affecting drug bioavailability, rate-limiting steps in drug absorption, physicochemical nature of the drug formulation factors affecting drug product performance, in vitro: dissolution and drug release testing, compendial methods of dissolution, alternative methods of dissolution testing,meeting dissolution requirements,problems of variable control in dissolution testingperformance of drug products. In vitro–in vivo correlation, dissolution profile comparisons, drug product stability,considerations in the design of a drug product

Unit 3

Pharmacokinetics: Basic considerations, pharmacokinetic models, compartment modeling: one compartment model- IV bolus, IV infusion, extra-vascular. Multi compartment model:two compartment – model in brief, non-linear pharmacokinetics: cause of non-linearity, Michaelis – Menten equation, estimation of kmax and vmax. Drug interactions: introduction, the effect of protein- binding interactions,the effect of tissue-binding interactions,cytochrome p450-based drug interactions,drug interactions linked to transporters.

Unit 4

Drug Product Performance, In Vivo: Bioavailability and Bioequivalence: drug product performance, purpose of
bioavailability studies, relative and absolute availability. methods for assessing bioavailability, bioequivalence studies, design and evaluation of bioequivalence studies, study designs, crossover study designs, evaluation of the data, bioequivalence example, study submission and drug review process. biopharmaceutics classification system, methods. Permeability: In-vitro, in-situ and In-vivo methods.generic biologics (biosimilar drug products),clinical significance of bioequivalence studies, special concerns in bioavailability and bioequivalence studies, generic
substitution.

Unit 5

Application of Pharmacokinetics: Modified-Release Drug Products, Targeted Drug Delivery Systems and Biotechnological Products. Introduction to Pharmacokinetics and pharmacodynamic, drug interactions. Pharmacokinetics and pharmacodynamics of biotechnology drugs. Introduction, Proteins and peptides, Monoclonal antibodies, Oligonucleotides, Vaccines (immunotherapy), Gene therapies.

REFERENCES

Biopharmaceutics and Clinical Pharmacokinetics by Milo Gibaldi, 4th edition,Philadelphia, Lea and Febiger, 1991
Biopharmaceutics and Pharmacokinetics, A. Treatise, D .M. Brahmankar and Sunil B. Jaiswal., VallabPrakashan, Pitampura, Delhi
Applied Biopharmaceutics and Pharmacokinetics by Shargel. Land YuABC, 2ndedition, Connecticut Appleton Century Crofts, 1985
Textbook of Biopharmaceutics and Pharmacokinetics, Dr. Shobha Rani R. Hiremath,Prism Book
Pharmacokinetics by Milo Gibaldi and D. Perrier, 2nd edition, Marcel Dekker Inc.,New York, 1982
Current Concepts in Pharmaceutical Sciences: Biopharmaceutics, Swarbrick. J, Leaand Febiger, Philadelphia, 1970
Clinical Pharmacokinetics, Concepts and Applications 3rd edition by MalcolmRowland and Thom~ N. Tozer, Lea and Febiger, Philadelphia, 1995
Dissolution, Bioavailability and Bioequivalence, Abdou. H.M, Mack PublishingCompany, Pennsylvania 1989
Biopharmaceutics and Clinical Pharmacokinetics, An Introduction, 4th edition,revised and expande by Robert. E. Notari, Marcel Dekker Inc, NewYork and Basel,1987.
Biopharmaceutics and Relevant Pharmacokinetics by John. G Wagner and M.Pemarowski, 1st edition, Drug Intelligence Publications, Hamilton, Illinois, 1971. 11. Encyclopedia of Pharmaceutical Technology, Vol 13, James Swarbrick, James. G.Boylan, Marcel Dekker Inc, New York, 1996.
Basic Pharmacokinetics,1 st edition,Sunil S JambhekarandPhilip J Breen,pharmaceutical press, RPS Publishing,2009.
Absorption and Drug Development- Solubility, Permeability, and Charge State, Alex Avdeef, John Wiley & Sons, Inc,2003.