04/19/23 1

BIOPHARMACEUTICS, NEW DRUG DELIVERY SYSTEMS & DEVICES 

A. S. Adebayo, Ph.D.

04/19/23 2

BIOPHARMACEUTICS COURSE CODE: PPHAR2213

LEVEL: 2

DURATION: 4 HOURS/week

CREDIT VALUE: 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.

04/19/23 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.

04/19/23 4

04/19/23 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.

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.

04/19/23 6

04/19/23 7

BIOPHARMACEUTICS

GENERAL OVERVIEW

04/19/23 8

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.

04/19/23 9

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.

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.

04/19/23 10

04/19/23 11

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.

04/19/23 12

Biopharmaceutical methodsThe application of knowledge

of drug release and transport across biomembrane to obtain the expected therapeutic effect from a product on administration to a patient.

04/19/23 13

Factors Influencing the time course of a drug in plasmaThe physical/chemical properties

of the drug

Type of dosage form of the drug

Composition and method of manufacture of the dosage form

04/19/23 14

Time-course of Drug in the Body

IN

AROUND

OUT

MouthLungsRectumSkinParenteral

AbsorptionDistribution

oRBC

oPLASMAPLASMA PROTEIN

WATER

MetabolismExcretion

oKidneysoLungsoSkinoOthers

04/19/23 15

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

04/19/23 16

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

04/19/23 17

Dosage form considerationThe 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.

04/19/23 18

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.

04/19/23 19

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.

04/19/23 20

Factors Influencing Drug Absorption

Can be categorized into 3:

Physiological factors

Physicochemical factors

Dosage form factors

04/19/23 21

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(1st 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

04/19/23 22

Rate limiting steps on systemic appearance of drugs

Nature of Drug Rate 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).

04/19/23 23

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.

04/19/23 24

Anatomy of G.I.T

04/19/23 25

Most significant sites of oral drug absorption

04/19/23 26

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).

04/19/23 27

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

04/19/23 28

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.

Wednesday 19 April 2023

BIOPHARMACEUTICS

29

THANK YOU FOR YOUR ATTENTION