Conquering low oral bioavailability issues in drug discovery and development

The optimization of bioavailability is critical to reducing underlying risks in drug development and increasing the likelihood of a drug candidate to have therapeutic benefit. This chapter summarizes current methodologies and approaches to overcome bioavailability issues in the drug discovery and development process. The first section covers the characterization of bioavailability, and focuses on the key parameters of solubility, permeability, and metabolic stability. The section also describes different approaches depending on the stage in the discovery-development continuum in which they are used. The focus of the second section is compound design strategies to optimize bioavailability, including rule-based guidelines that have been developed and applied to drug design. The third section covers the optimization and management of bioavailability through formulation or other technologies. The overall goal of the chapter is to provide useful information covering current approaches to optimize oral bioavailability to increase the likelihood of success in drug discovery and development.