Bioavailability from pharmaceutical dosage forms

Abstract

The last few years have witnessed a concentration of interest in the effectiveness of pharmaceutical dosage forms. This interest has arisen from a growing awareness that the efficacy of an otherwise acceptable drug can be severely affected by insufficient attention to the manner of its presentation for administration by different manufacturers. This has found expression in the concept of bioavailability.

Strictly, bioavailability is only assessable in terms of availability of the drug substance at the actual site of action. For various reasons, however, direct measurement of bioavailability is frequently not possible in human subjects. Its assessment, therefore, usually rests on the measurement of secondary parameters of which blood levels and urinary excretion data are the most common.

The route of administration adopted for any drug depends on a combination of the clinical requirement, the physicochemical properties of the drug substance, and the extent to which these can be modified by formulation. Within the limitations imposed by such considerations, bioavailability depends principally on the skill of the formulator and his assessment of the physiological parameters that affect the absorption, transport, metabolism and excretion of the drug from the body. Once the product is formulated, standardisation of its production depends on the ability of the production pharmacist and his quality controller to specify and keep check on the parameters necessary to achieve uniformity from one batch to the next.

Physiological factors, which affect blood levels and tissue availability of drug substances, are considered. These include plasma and tissue protein binding, cell binding, lipid deposition and metabolism, and assessment of the interplay between them. The physicochemical properties that affect their availability from oral dosage forms, aerosols and topical preparations are examined with particular reference to factors affecting rates of solution of substances with low water solubility. Crystallinity, polymorphism, particle size, wettability and ease of dissolution are examined from this point of view.