Presented by:

DIPANKAR DAS M.PHARM (PH.CEUTICS)

 Bioavailability is defined: Bioavailability is a measurement of the extent of a therapeutically active drug that reaches the systemic circulation and is available at the site of action. OR The extent and rate at which its active moiety is delivered from pharmaceutical form and becomes available in the systemic circulation.

Pharmacokinetics
conc. vs time
Conc.(mg/L)
0.0 0 25

Time (h)

Drug Product Drug in Blood Excretio n Distribution to Tissue and Receptor sites Metabolism

Why do we care about BIOAVAILABILITY?

The true dose is not the drug swallowed; BUT is the drug available to exert its effect.

Absorption, Survive metabolism, Dissolution, Dosage form or drug may not dissolve readily, Drug may not be readily pass across biological membranes, Drug may be extensively metabolized during absorption process (first-pass, gut wall, liver), Important component of overall variability, etc.

How Absorption affects Bioavailability?

 Absorption is defined as the process by which a drug proceeds from the site of administration to the site of measurement. Drugs are frequently administered extravascularlyoral, sublingual, intramuscular, topical, patches, inhalation, etc. Absorption is a prerequisite for a drug to exert its pharmacologic effect (other than local effect).

Several possible factors, which are effect the absorption. Drug Product Drug in Blood Excreti
Absorption

Distribution to Tissue and Receptor sites Metabolism

They are classified as--Physiological Factor, Physicochemical Factor, Pharmaceutical Factor.

How Drug Metabolism affects Bioavailability?

 Anatomical Considerations
Gut Lumen Portal Vein Liver Gut Wall Systemic Circulation
Metabolism

Metabolism

Reactions Catalyzed by Drug metabolizing enzymes Oxidative reactions (Phase I) dealkylation hydroxylation oxidation Deamination Conjugation reactions (Phase II) glucuronidation glutathione conjugation sulfation acetylation

Drug metabolism/Biotransformation

Bioavailability factor (F)

It is the relative extent of absorption of a drug from a drug product, and this may be determined from the expression. Bioavailability of product F = -----------------------------------Bioavailability of standard AUC of drug product = --------------------AUC of standard To calculate the amount of drug absorbed, the administered dose should be multiplied by bioavailability factor.

 Ex : The bioavailability of digitoxin is estimated to be 0.62 for orally administered tablets. This means that if 250mg of digitoxin is given orally, the effective or absorbed dose (155) can be calculated by multiplying the administered dose F. Objectives of bioavailability Control of quality of the formulation in order to determine the influence of various processing / manufacturing factors, storage and stability. Study of influence of various expients on the efficiency of absorption of active drug ingredients in the body. Development of suitable dosage form for a new drug. Development of new formulation for existing drugs.

Types of bioavailability
Absolute bioavailability. Relative bioavailability. Absolute bioavailability (Fa) Absolute bioavailability may be measured by comparing the total amount of intact drug that reaches the systemic circulation after administration of a known dose of the drug in the dosage form via an equivalent dose of the drug in the form of an intravenous bolus injection. An intravenous bolus injection of the drug is used as reference to compare the systemic availability of the drug administered via another absorption site.

 For equivalent doses of administered drug,

If different doses of the drug are administered:

A drug given by the intravenous route will have an absolute bioavailability of 1 (F=1) while drugs given by other routes usually have an absolute bioavailability of less than one.

 Relative bioavailability (Fr) In case of drugs which cannot be administered in the form of an intravenous bolus injection, the relative bioavailability is determined rather absolute bioavailability. When equivalent doses of a test and recognized standard dosage form are administered by the same route of administration to the same subject on different occasions,

Theory of bioavailability:
For drugs excreted unchanged after intravenous administration the peak plasma concentration is described by following equations:

Methods of enhancement of bioavailability

Particle size reduction . Soluble Matrix carrier. Solid dispersion. Use of surface active agents. Inclusion complexes. Modification of the drug molecular structure. Partition coefficient .

 Particle size reduction

 Soluble Matrix carrier

 Solid dispersion

 Use of surface active agents

 Inclusion complexes

 Modification of the drug molecular structure

 Partition coefficient

 References: Fundamentals of biopharmaceutics and pharmacokinetics. Tipinis. Fundamentals of biopharmaceutics and pharmacokinetics. Venkateshwarulu. Fundamentals of biopharmaceutics and pharmacokinetics. Madan. Biopharmaceutics and pharmacokinetics. D.M.Brahmankar. Sunil B Jaiswal. Internet Source