Physical and biological considerations for the use of nonaqueous solvents in oral bioavailability enhancement

This review addresses the use of nonaqueous solvents as components of oral formulations in discovery and preclinical studies. Pharmacology, pharmacokinetic, and safety studies are frequently conducted with solution formulations that use a solvent to solubilize poorly aqueous soluble drugs. The physical chemical basis for solubilization and the precipitation of solubilized drug following administration both contribute to the utility of nonaqueous solvent solutions as oral vehicles. While many of these solvents are considered nontoxic, they are not completely inert biologically. The effects of common nonaqueous solvents on the structural integrity of the epithelia, the inherent permeability of and flux across the GI membrane, the activity of efflux and metabolic enzymes, and the effects on GI motility and GI transit times will be described through an examination of available literature. The practical relevance of these factors to the development of early formulations will be examined critically and suggestions made for the suitability of nonaqueous solvents for a variety of purposes. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1071-1088, 2008