Development and application of a high-throughput formulation screening strategy for oral administration in drug discovery

Abstract

For small-molecule drugs the oral route of administration remains the most popular means of delivery for many indications. Optimizing oral bioavailability is, therefore, of critical importance in both drug discovery and development. However, while formulation development is routinely evaluated in clinical development, limited attention appears to be focused on improving exposure following oral delivery in early preclinical testing. The reasons for this appear to be limited compound availability and the requirement for a very rapid turnaround time. While some effort has been made to address solubility for intravenous formulation development, there is limited information available regarding formulation screening for oral delivery in drug discovery and preclinical development. In this brief article, we provide some details on our high-throughput, low compound requirement screen for oral formulation development. This screen has direct application in lead identification and development. The assay has been validated across multiple chemical series targeting different therapeutic areas, and is routinely applied with significant success in improving oral bioavailability.