Formulations and Related Activities for the Oral Administration of Poorly Water-soluble Compounds in Early Discovery Animal Studies
An overview of frequently applied approaches
Beate Bittner and Richard Jolyon Mountfield
Pharmaceuticals Division, DMPK Discovery Support, F. Hoffmann-La Roche Ltd., Basel (Switzerland)
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.
Key words Bioavailability, oral · Drug discovery · Drug solubility · Exploratory drug formulations · Prodrugs · Salts (of drugs)
pharmind 2002, Nr. 9, Seite 985