Selection of Solubility Enhancement Technologies for S-892216, a Novel COVID-19 Drug Candidate.

Background/Objectives: S-892216 is a poorly water-soluble drug developed as a novel oral treatment for 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. Methods: The solubility enhancement technology was selected by considering physicochemical factors such as stability and oral absorption, along with patient and customer acceptability. Results: Pharmacokinetics study in rats revealed that both the polyethylene glycol 400 oral solution and polyvinylpyrrolidone-vinyl acetate (PVPVA) amorphous solid dispersion powder suspension showed almost 100% oral bioavailability. Therefore, they can be proposed as clinical formulations for Ph1 studies. PVPVA solid dispersion tablets were 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. Conclusions: This study demonstrates that multiple solubility enhancement technologies can be adopted for S-892216 development, and amorphous solid dispersion technology was selected for commercialization.