1. BIOPHARMACEUTICS Adapted by : S. Campbell-Elliott M. Pharm. Sc. Prepared by : A.S. Adebayo, Ph.D. & M. A Williams. M.S.

10. Schematic illustration of the steps involved in the appearance of intact drug in systemic circulation following oral administration of a tablet STOMACH (Gastric content. pH 1-3) SMALL INTESTINE (Intestinal cont. pH 5-7) Tablet Granules Fine particles Dissolution Drug in solution Tablet Granules Fine particles Dissolution Drug in solution Absorption Intact drug Liver Intact Drug in systemic Circulation Pharmacologic effect Intestinal metabolism Metabolites Urine Hepatic Metabolism (1 st Pass Effect) Disintegration Deaggregation

11. Rate Limiting Steps of Absorption Rate of metabolism of drug during its initial passage through the liver (i.e. First-pass effect). Rate at which drug is metabolized by the enzymes in the intestinal mucosal cells en route into mesenteric blood vessels Rate of gastric emptying into small intestine Other factors Rate of release from the dosage form Dosage Design Rate at which drug crosses membrane of the GIT High aqueous solubility Rate of dissolution in gastrointestinal fluid Poor aqueous solubility Rate Limiting Step Nature of Drug

12. Physiological Factors Affecting Oral Absorption

13. Fate of a Drug Product

14. Simplified Model of Membrane

15. Davson-Danielli Model

30. Increase in Surface Surface Area Structure (relative to cylinder) sq cm simple cylinder 1 3,300 Folds of Kerckring 3 10,000 Villi 30 100,000 Microvilli 600 2,000,000