S-892216 anhydrous crystal exhibited extremely low water solubility, ranging from 0.61 to 1.08 µg/mL, under all pH conditions (Table ). These values are below the solubility threshold of 10 µg/mL, which is the absorption criterion for a drug orally administered at the dose of 1 mg/kg, as stated by Lipinski et al., potentially hindering absorption. The BA of S-892216 anhydrous crystal capsules orally administered to dogs was 22.2% (Fig. and Table ). This value is also below the target BA of 70% or more, which is defined as high absorption. Low BA can present serious problems, such as increased dose requirement, absorption variability, and unexpected dose-response relationships. Therefore, we decided to pursue formulation approaches to enhance drug solubility and oral absorption.