Course Summary: Biopharmaceutics

Overall Goal: This course explores the interrelationship between the physicochemical properties of a drug, the design and manufacture of its dosage form, and the route of administration on the rate and extent of systemic drug absorption. The ultimate aim is to understand how to design drug products that deliver the active pharmaceutical ingredient (API) to the site of action effectively and consistently.

Key Topics Covered:

1. Introduction to Biopharmaceutics:

   • Definitions, scope, and importance in drug development and therapy.

   • Relationship with pharmacokinetics, pharmacology, and pharmaceutical technology.

   • Concept of drug product performance and therapeutic efficacy.

2. Physicochemical Properties of Drugs Relevant to Absorption:

   • Solubility and Dissolution: Factors affecting them (pH, pKa, salt form, polymorphism, particle size, Noyes-Whitney equation).

   • Permeability: Partition coefficient (Log P), ionization, molecular size, hydrogen bonding.

   • Stability: Chemical and physical stability of the drug in the gastrointestinal (GI) tract.

   • Biopharmaceutics Classification System (BCS).

3. Biological Membranes and Drug Transport:

   • Structure and properties of biological membranes (e.g., GI mucosa).

   • Mechanisms of drug transport across membranes:

     • Passive diffusion (Fick's First Law)

     • Carrier-mediated transport (active transport, facilitated diffusion)

     • Vesicular transport (endocytosis, pinocytosis)

     • Pore transport

     • Efflux transporters (e.g., P-glycoprotein) and their impact.

4. Drug Absorption from Different Routes of Administration:

   • Oral Absorption (Major Focus):

     • Anatomy and physiology of the GI tract relevant to drug absorption (pH, surface area, blood flow, transit time, gastric emptying, intestinal motility).

     • Factors affecting oral absorption: drug properties, formulation factors, physiological factors (food effects, disease states, age).

     • First-pass metabolism (hepatic and intestinal).

   • Other Routes: Parenteral (IV, IM, SC), Buccal/Sublingual, Rectal, Transdermal, Pulmonary, Nasal, Ocular – biopharmaceutical considerations for each.

5. Dosage Form Design and Biopharmaceutical Considerations:

   • Solutions, Suspensions, Emulsions: Biopharmaceutical advantages and disadvantages.

   • Solid Dosage Forms (Tablets, Capsules):

     • Role of excipients (disintegrants, binders, lubricants, fillers, etc.).

     • Manufacturing processes and their impact on drug release (e.g., compression force).

     • Disintegration, deaggregation, and dissolution processes.

   • Modified-Release Drug Delivery Systems:

     • Rationale and design (e.g., sustained-release, controlled-release, delayed-release, enteric-coated, targeted delivery).

     • Mechanisms of drug release from these systems.

6. Dissolution Testing and In Vitro-In Vivo Correlation (IVIVC):

   • Theories and models of drug dissolution.

   • Official (pharmacopeial) and unofficial dissolution testing methods and apparatus.

   • Factors affecting dissolution rate.

   • Concept and importance of IVIVC; levels of correlation.

7. Bioavailability (BA) and Bioequivalence (BE):

   • Definitions: bioavailability (rate and extent), absolute vs. relative bioavailability.

   • Pharmacokinetic parameters for assessing BA (AUC, Cmax, Tmax).

   • Methods for assessing bioavailability.

   • Bioequivalence studies: purpose, design, statistical evaluation.

   • Regulatory requirements for BA/BE studies (e.g., for generic drug approval).

   • Factors affecting bioavailability.

8. Factors Affecting Drug Absorption and Bioavailability:

   • Physiological factors (age, disease, food, GI pH, gastric emptying).

   • Physicochemical factors (drug solubility, permeability, stability).

   • Formulation factors (dosage form, excipients, manufacturing variables).

   • Drug interactions (drug-drug, drug-food).

9. Regulatory Aspects:

   • Role of biopharmaceutics in new drug application (NDA) and abbreviated new drug application (ANDA).

   • Biowaivers.

Learning Outcomes:
Upon successful completion of a biopharmaceutics course, students should be able to:

• Understand the fundamental principles governing drug absorption.

• Identify and analyze how drug properties, dosage form characteristics, and physiological factors influence drug release and absorption.

• Interpret dissolution data and understand its relevance to in vivo performance.

• Comprehend the concepts of bioavailability and bioequivalence and their regulatory significance.

• Apply biopharmaceutical principles to the design and evaluation of drug delivery systems.