There are some strategies to enhance the solubility and absorption of poorly water-soluble drugs. One of the standard approaches is the crystal engineering of drug substances, namely the formation of salts, solvates, and co-crystals. By integrating micronization with crystal engineering, for example, by using a jet mill, it becomes possible to manufacture tablets or capsules using conventional manufacturing processes. When crystal engineering fails, formulation-based approaches may be explored to enhance solubility. Popular formulations include amorphous solid dispersions, which stabilizes the amorphous form of the drug, and oral solutions such as lipid-based formulations, which maintains the dissolved form of the drug. These technologies have been in practical use for more than a decade, supported by numerous research findings and multiple commercial products. Pharmaceutical companies consider multiple factors beyond just improving oral absorption in the selection of appropriate solubility enhancement technologies. It is necessary to conduct clinical studies in a sequential manner during drug development. Phase 1 clinical studies often employ assessments of absorption, distribution, metabolism, and excretion (ADME). Pharmaceutical companies sometimes need to develop a dose-flexible formulation for human ADME studies only. In the development of to-be-marketed formulations, the shelf-life of the product, which is determined from stability data, impacts supply chain costs and customer satisfaction. Amorphous solid dispersions and oral solutions are promising formulations that enhance solubility, although they tend to be chemically unstable compared with the crystalline form. From another perspective, the dosage form can affect the ease of ingestion, namely swallowing, which can in turn impact patient acceptability. Although numerous research studies on solubility enhancement technologies have been reported, to the best of our knowledge, few studies have discussed the industrial applicability of these technologies considering the factors mentioned above. CoV-2. During the drug discovery stage, we found that S-892216 anhydrous crystal exhibits very low water solubility and low oral absorption. Here, we describe the approach by which we evaluated the ADME of various formulations of S-892216 and developed tablets for the clinical development program of S-892216.