Route-specific challenges in the delivery of poorly water-soluble drugs

Abstract

Poor aqueous solubility of new chemical entities presents various challenges in the development of effective drug-delivery systems for various delivery routes. Poorly soluble drugs that are delivered orally commonly result in low bioavailability and are subject to considerable food effects. In addition, poorly soluble drugs intended for parenteral delivery generally have to be solubilized with large amounts of co-solvents and surfactants, oftentimes resulting in adverse physiological reactions. Ocular delivery of poorly soluble drugs is challenging due to the absorption barriers and clearance mechanisms. Poorly soluble drugs administered nasally are limited by a relatively small administered volume, the geometry of the nasal cavity and the strict safety requirements of the excipients used in the formulation. Finally, successful formulation design of poorly soluble drugs intended for pulmonary administration is hindered by the limited number of excipients generally recognized as safe for this route of delivery and the anatomical and physiological clearance mechanisms found in the airways. In summary, this chapter reviews the specific challenges faced in the delivery of poorly water-soluble drugs via oral, parenteral, and pulmonary administration.