Brief overview of solubility methods: Recent trends in equilibrium solubility measurement and predictive models

Solubility is a crucial physicochemical parameter affecting the whole process of drug discovery and development. Thus, understanding of the methods and concepts to measure and predict this propensity are of utmost importance for the pharmaceutical scientist. Despite their inherent limitations, kinetic solubility screening methods became routine assays by mimicking bioassay conditions and guiding the lead optimization process. In contrast, thermodynamic solubility methods show a clear evolution: miniaturized high throughput assays coupled to analytical techniques such as solid-state characterization, ultra performance liquid chromatography, or polychromatic turbidimetry, have been developed, thereby enabling a more complex physicochemical profiling at the early discovery stage. Solubility prediction still poses a significant challenge at the industrial level. Classification and critical evaluation of recent in silico models are provided. Discussion of experimental and computational methods: was based on relevant industrial references.