Bioavailability and Bioequivalence

Bioavailability and Bioequivalence

The therapeutic effectiveness of a drug depends upon the ability of the dosage form to deliver the medicament to its site of action at a rate and amount sufficient to elicit the desired pharmacological response. This attribute of the dosage form is referred to as physiological availability, biological availability or simply, bioavailability. For most drugs, the pharmacological response can be related directly to the plasma levels. Thus, the term bioavailability is defined as the rate and extent (amount) of absorption of unchanged drug from its dosage form. It is an absolute term. The rate or rapidity with which a drug is absorbed is an important consideration when a rapid onset of action is desired as in the treatment of acute conditions such as asthma attack, pain, etc. A slower absorption rate is, however, desired when the aim is to prolong the duration of action or to avoid the adverse effects. On the other hand, extent of absorption is of special significance in the treatment of chronic conditions like hypertension, epilepsy, etc.

If the size of the dose to be administered is same, then bioavailability of a drug from its dosage form depends upon 3 major factors:

1. Pharmaceutical factors related to physicochemical properties of the drug and characteristics of the dosage form.

2. Patient related factors.

3. Route of administration.

The former two factors have been dealt with comprehensively in Chapter 2 on Absorption of Drugs. The influence of route of administration on drug's bioavailability is generally in the following order with few exceptions:

Parenteral > Oral > Rectal > Topical

Within the parenteral route, intravenous injection of a drug results in 100% bioavailability as the absorption process is bypassed. However, for reasons of stability and convenience, most drugs are administered orally. In such cases, the dose available to the patient, called as the bioavailable dose, is often less than the administered dose. The amount of drug that reaches the systemic circulation (i.e. extent of absorption) is called as systemic availability or simply availability. The term bioavailable fraction F, refers to the fraction of administered dose that enters the systemic circulation.

F = Bioavailable dose / Administered dose               (11.1)

Objectives of Bioavailability Studies

Bioavailability studies are important in the —

1. Primary stages of development of a suitable dosage form for a new drug entity to obtain evidence of its therapeutic utility.

2. Determination of influence of excipients, patient related factors and possible interaction with other drugs on the efficiency of absorption.

3. Development of new formulations of the existing drugs.

4. Control of quality of a drug product during the early stages of marketing in order to determine the influence of processing factors, storage and stability on drug absorption.

5. Comparison of availability of a drug substance from different dosage forms or from the same dosage form produced by different manufacturers.