Automated assays for thermodynamic (equilibrium) solubility determination

Abstract

Solubility is a crucial physicochemical property for drug candidates and is important in both drug discovery and development. Poor solubility is detrimental to absorption after oral administration and can mask compound activity in bioassays in various ways. Hence, solubility liabilities should ideally be identified as early as possible in the drug development process. With the increasing number of compounds as potential drug candidates, automated thermodynamic solubility assays for high throughput screening enabling rapid evaluation of a large number of compounds are becoming increasingly important. This review discusses the current status of the most widely used automated assays for thermodynamic solubility, followed by recent high throughput measurements of properties related to solubility (e.g. dissolution rate and supersaturation) and a brief overview of predictive computational methods for thermodynamic solubility reported in the literature.