Selection of Solubility Enhancement Technologies Depending on Developmental Stage: A Case Study of S-892216, a Poorly Water-Soluble Drug

S-892216 is a poorly water-soluble drug developed as a novel oral treatment of COVID-19, although its oral absorption is low. For Phase 1 (Ph1) studies and commercial use, both oral solution and solid dispersion technologies are evaluated to enhance drug solubility. The solubility enhancement technology was selected by considering physicochemical factors such as stability and oral absorption, along with patient and customer acceptability. Pharmacokinetics study in rats revealed that both the polyethylene glycol 400 oral solution and polyvinylpyrrolidone-vinyl acetate (PVPVA) solid dispersion powder suspension showed almost 100% oral bioavailability. Therefore, they can be proposed as clinical formulations for Ph1 studies. PVPVA solid dispersion tablets developed as a to-be-marketed formulation showed higher bioavailability in dogs than the anhydrous crystal formulation. Additionally, the stability of the developed solid dispersion tablet was acceptable. This study demonstrates that multiple solubility enhancement technologies can be adopted for S-892216 development.