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BIOPHARMACEUTICS, NEW DRUG DELIVERY SYSTEMS & DEVICES A. S. Adebayo, Ph.D. 5/23/2017 1 BIOPHARMACEUTICS COURSE CODE: LEVEL: DURATION: CREDIT VALUE: 5/23/2017 PPHAR2213 2 4 HOURS/week 4 2 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. 5/23/2017 3 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. 5/23/2017 4 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. 5/23/2017 5 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. 5/23/2017 6 BIOPHARMACEUTICS GENERAL OVERVIEW 5/23/2017 7 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. 5/23/2017 8 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. 5/23/2017 9 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. 5/23/2017 10 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. 5/23/2017 11 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. 5/23/2017 12 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 5/23/2017 13 Time-course of Drug in the Body AROUND IN Mouth Lungs Rectum Skin Parenteral OUT Absorption Distribution oRBC oPLASMA PLASMA PROTEIN Metabolism Excretion oKidneys oLungs oSkin oOthers WATER 5/23/2017 14 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 5/23/2017 15 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 5/23/2017 16 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. 5/23/2017 17 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. 5/23/2017 18 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. 5/23/2017 19 Factors Influencing Drug Absorption Can be categorized into 3: Physiological factors Physicochemical Dosage 5/23/2017 factors form factors 20 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 Tablet Disintegration Granules Granules Deaggregation Fine particles Fine particles Dissolution Dissolution Drug in solution Drug in solution Absorption Intact drug Liver Intact Drug in systemic Circulation 5/23/2017 Intestinal metabolism Hepatic Metabolism (1st Pass Effect) Metabolites Urine 21 Pharmacologic effect Rate limiting steps on systemic appearance of drugs Nature of Drug Rate limiting step Drug of very poor Rate of dissolution in gastrointestinal fluid aqueous solubility Drug of high aqueous Rate at which drug crosses git membrane solubility 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 5/23/2017 Rate of metabolism of drug during its initial passage through 22 the liver (i.e. First-pass effect). 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. 5/23/2017 23 Anatomy of G.I.T 5/23/2017 24 Most significant sites of oral drug absorption 5/23/2017 25 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). 5/23/2017 26 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 5/23/2017 27 Assignments Attempt a diagramatic illustration of the gastrointestinal tract and clearly identify the regions’ physiology by: 5/23/2017 pH Volume of fluids Length or duration of stay of ingested substance Thickness of the membranes Blood supply Enzyme presence & abundance. 28 THANK YOU FOR YOUR ATTENTION BIOPHARMACEUTICS Tuesday, 23 May 2017 29