Current screening, design, and delivery approaches to address low permeability of chemically synthesized modalities in drug discovery and early clinical development

A drug’s permeability across biological membranes is a key property associated with the successful development of an orally absorbed drug candidate. Although a variety of methods are available for predicting and assessing permeability, some are more preferred than others at specific stages of drug discovery and development across the pharmaceutical industry. Permeability measurements may be interpreted differently depending on the chosen method. Herein, we present a refreshed perspective on the screening approaches and philosophy in permeability evaluation, from early drug discovery to early clinical development. Additionally, we review and discuss chemical design and drug delivery technologies that can be leveraged to overcome permeability challenges, which are increasingly being used with emerging modalities.