Formulations and related activities for the oral administration of poorly water-soluble compounds in early discovery animal studies: An overview of frequently applied approaches. Part 1

An increasing number of compounds that are investigated in industrial drug discovery are characterized as having low aqueous solubility. Combined with other unfavorable physicochemical characteristics, poor solubility can lead to low oral bioavailability. Even though low systemic exposure may be overcome with suitable formulation principles, an increase in oral bioavailability in early animal experiments due to the co-administered dosing vehicle may not always be desirable. Since most animal experiments in drug discovery are performed in order to rank compounds according to their intrinsic pharmacodynamic and pharmacokinetic properties, an impact of the formulation on these parameters should either be excluded or understood. This review summarizes common formulation approaches and related activities such as salt or prodrug screening, performed in order to orally administer these types of compounds to laboratory animals and, in some instances, to eventually increase their systemic exposure. In addition, the suitability of these approaches in different stages of the drug discovery process from lead identification up to clinical candidate selection is discussed.