2. 10/1/20151 BIOPHARMACEUTICS, NEW DRUG DELIVERY SYSTEMS & DEVICES A. S. Adebayo, Ph.D.

3. 10/1/20152 BIOPHARMACEUTICS  COURSE CODE:PPHAR2213  LEVEL: 2  DURATION: 4 HOURS/week  CREDIT VALUE: 4

4. COURSE DESCRIPTION  Biopharmaceutics course seeks to educate and train candidates in the principles underlining drug absorption, distribution, metabolism and excretion (ADME) following its administration to human or animal subjects.  The course places emphasis on the dependence of drug absorption on the physical and chemical nature of drug substances, the effect of dosage form in which it is designed and the factors related to the physiologic and pathologic conditions of the subjects to which it is administered. 10/1/20153

5. COURSE DESCRIPTION (Cont.)  The aim is to develop in the candidate the ability to integrate all these factors holistically in optimizing therapeutic benefit to the patient while minimizing adverse or untoward effects of medicinal products.  In addition, the course would train the candidates in novel delivery technologies that are currently being employed for enhancing drug delivery to various targets in the body. 10/1/20154

6. 5 OBJECTIVES  On completion of the course the student should be able to: Discuss factors that influence absorption, distribution, metabolism and excretion of the drugs in the body. Explain how dosage forms and presentations may affect the delivery of drug substances to various parts of the body, particularly the site of action Explain the concepts of bioavailability, bioequivalence and drug products selection and substitution.

7. COURSE OBJECTIVES (Cont.) Describe the drug interactions, which occur during absorption, distribution and elimination of drugs and how these interactions influence the therapeutic effects of particular drugs. Describe the features and explain the design and mechanisms of drug delivery via some novel delivery systems. 10/1/20156

8. 7 BIOPHARMACEUTICS GENERAL OVERVIEW

9. 10/1/20158 General Overview/Definitions  Biopharmaceutics is concerned with the relationship between the physicochemical properties of a drug in a dosage form and the observed therapeutic response after its administration.  Biologic response Expressed as the alteration of the biologic process existing before the drug was administered Its magnitude is related to the concentration of drug reaching the receptor site. The observed biological effect of drug in a dosage form = inherent pharmacological activity of the drug + its ability to reach the receptor site in appropriate concentration + MRT  Thus, the onset, intensity and duration of therapeutic effect of most drugs depend on factors of the biological system + the dosage form.

10. 10/1/20159 General Overview/Definitions (Cont.)  These factors play important role in: bringing the drug to the biological site in the body in quantities required + sustaining it at that concentration for the desired length of time + getting the drug out of the site after it has performed the desired effect.  Hence, the scope of biopharmaceutics is comprised of the path the drug must take from the dosage form to the site of action and the factors encountered en-route.

11. General Overview/Definitions (Cont.)  Objectives of Biopharmaceutics course are to gain a basic understanding of the processes of drug absorption, distribution and elimination + the potentials of dosage form effects on these processes that can be applied to optimization of therapeutic benefit for a patient.  Dosage form of a drug exerts its major influence on the absorption process, thus emphasis is usually placed on drug absorption. 10/1/201510

12. 10/1/201511 Biopharmaceutics  Biopharmaceutics simply means “the effects of dosage form and route of administration on the biological effect of a drug” -study of factors influencing the dissolution of drug from dosage form into biological fluids at the site of absorption and the transfer of the dissolved drug across biomembrane into the systemic circulation.

13. 10/1/201512 Biopharmaceutical methods  The application of knowledge of drug release and transport across biomembrane to obtain the expected therapeutic effect from a product on administration to a patient.

14. 10/1/201513 Factors Influencing the time course of a drug in plasma  The physical/chemical properties of the drug  Type of dosage form of the drug  Composition and method of manufacture of the dosage form

15. 10/1/201514 Time-course of Drug in the Body IN AROUND OUT Mouth Lungs Rectum Skin Parenteral  Absorption  Distribution o RBC o PLASMA  PLASMA PROTEIN  WATER Metabolism Excretion o Kidneys o Lungs o Skin o Others

16. 10/1/201515 Factors Influencing the time course of a drug in plasma (Cont.)  The size of the dose and frequency of administration of the dosage form  Site of absorption of the administered drug  Co-administration of other drugs  Type of food taken by the patient

17. 10/1/201516 Factors Influencing the time course of a drug in plasma (Cont.)  The disease state of the patient that may affect drug absorption, distribution and elimination of the drug  The age of the patient.  The genetic composition of the patient

18. 10/1/201517 Dosage form consideration  The particle size of the drug  Its chemical nature e.g. salt, weak acid or base, ester form, complex form, etc.  The physical state of the drug e.g. crystalline, amorphous, hydrate, polymorphs, etc.

19. 10/1/201518 Dosage form consideration (Cont.)  The inert ingredients e.g. diluents, binders, disintegrants, suspending agents, coating agent, etc.  Type of dosage form in the traditional sense of it e.g. tablet, capsule, solution, suspension, suppository, etc.

20. 10/1/201519 Bioavailability: rate & extent  Bioavailability deals with the transfer of drug from its site of administration into the body system and this is manifested by its appearance in general circulation.  Because a transfer system is involved, bioavailability is characterized by the rate of transfer and the total amount transferred.

21. 10/1/201520 Factors Influencing Drug Absorption  Can be categorized into 3: Physiological factors Physicochemical factors Dosage form factors

22. 10/1/201521 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 Schematic illustration of the steps involved in the appearance of intact drug in systemic circulation following oral administration of a tablet

23. 10/1/201522 Rate limiting steps on systemic appearance of drugs Nature of DrugRate limiting step Drug of very poor aqueous solubility Rate of dissolution in gastrointestinal fluid Drug of high aqueous solubility Rate at which drug crosses git membrane Controlled-, modified-, etc release formulation Rate of release from the dosage form Other general rate limiting factors Rate of gastric emptying into small intestine (e.g. enteric coated tablets) Rate at which drug is metabolized by the enzymes in the intestinal mucosal cells en route into mesenteric blood vessels Rate of metabolism of drug during its initial passage through the liver (i.e. First-pass effect).

24. 10/1/201523 Structure of the Gastro-intestinal Tract  The g.i.t. consists of 3 anatomical regions:  Stomach  Small intestine  Large intestine (colon).  The small intestine comprises:  Duodenum  Jejunum  Ileum. As a drug moves through these three regions, it encounters different environments differing in pH, type of enzymes, electrolytes, fluidity and surface features….. All these can influence drug absorption.

25. 10/1/201524 Anatomy of G.I.T

26. 10/1/201525 Most significant sites of oral drug absorption

27. 10/1/201526 Anatomy of G.I.T.  The g.i.t. is basically a hollow muscular tube composed of 4 concentric layers of tissues, namely the:  Mucosa (mucous membrane)  Sub-mucosa  Muscularis externa, and  Serosa (the outermost layer, next to the peritoneal cavity).

28. 10/1/201527 The Mucosa  Mucosa is the most important to drug absorption.  It contains the cellular membrane through which a drug must pass in order to reach the blood (or lymph).  The mucosa is itself made of 3 layers: Lining epithelium Lamina propria Muscularis mucosa

29. 10/1/201528 Assignments  Attempt a diagramatic illustration of the gastrointestinal tract and clearly identify the regions’ physiology by: pH Volume of fluids Length or duration of stay of ingested substance Thickness of the membranes Blood supply Enzyme presence & abundance.

30. Thursday, 01 October 2015 BIOPHARMACEUTICS 29 THANK YOU FOR YOUR ATTENTION