The Rational Selection for Solubilized Formulation Technologies Utilizing Physicochemical Properties

Abstract

Enhancing the solubility of poorly water-soluble oral small-molecule drugs remains a critical challenge in the pharmaceutical industry, particularly during the early stages of drug development when selecting solubilized formulation technologies. This difficulty largely stems from the absence of objective indicators for comparing formulations. This study aimed to establish the selection indicators for solubilized formulation technologies based on applicable formulation preparation among amorphous solid dispersion (ASD), cyclodextrin (CD), lipid-based formulation (LBF), and nanocrystal (NC), utilizing the overall molecular properties, such as molecular weight, melting point (T_m), Log P, and polar surface area (PSA) in the marketed oral drugs employing solubilized formulation technologies. Single-property plots of the selected properties revealed the regions of higher or lower frequency in the selected molecular properties. The multiple property plot with T_m and the combined property of normalized Log P and PSA identified a specific area as the optimal range for selecting ASD, LBF, and NC, while excluding CD. These findings are expected to function as guide indicators that enable the rational selection of formulation technologies and serve as a foundational approach to accelerating development timelines based on molecular properties available during the early stages of drug development.