Laboratory-based Prediction of Drug Biopharmaceutical Properties

Abstract

Bioavailability (BA), i.e. the amount of drug that is absorbed from the gut and delivered intact to the systemic circulation, is a main concern in the drug development process. Pharmaceutical scientists are striving to achieve as high BA as possible (one that approaches that after intravenous bolus). Biopharmaceutics is concerned with the physicochemical properties of a drug, the formulation in which the drug is placed as well as the physiology of the human being that would eventually lead to a high BA. The key biopharmaceutical properties are: solubility of drug in the gastrointestinal (GI) fluids and its permeability through the intestinal mucosa. The goal of connecting in vitro and in vivo behaviour of a drug product is an endless goal for research, industry and regulatory societies. It is important to highlight how far the science has progressed in this regard but also how far it has to go to achieve this goal. Early in the drug discovery process, the favourable biopharmaceutical drug properties were acknowledged especially after these properties were represented by the renowned Biopharmaceutical Classification System (BCS). The guidelines for the BCS were introduced by the Food and Drug Administration (FDA) to simplify the production of generic drugs (FDA 2000). The drug discovery process was inspired by the BCS to adopt the structure-property relationship (SQR) rather than the traditional paradigm of structure-activity relationship (SAR). In this context, the lead structures in the drug discovery process were not only optimized with regard to their pharmacological properties but equally important, their biopharmaceutical properties.