title: Estimating the Aqueous Solubility of Pharmaceutical Hydrates.
abstract: Estimation of crystalline solute solubility is well documented throughout the literature. However, the anhydrous crystal form is typically considered with these models, which is not always the most stable crystal form in water. In this study, an equation which predicts the aqueous solubility of a hydrate is presented. This research attempts to extend the utility of the ideal solubility equation by incorporating desolvation energetics of the hydrated crystal. Similar to the ideal solubility equation, which accounts for the energetics of melting, this model approximates the energy of dehydration to the entropy of vaporization for water. Aqueous solubilities, dehydration and melting temperatures, and log P values were collected experimentally and from the literature. The data set includes different hydrate types and a range of log P values. Three models are evaluated, the most accurate model approximates the entropy of dehydration (ΔSd) by the entropy of vaporization (ΔSvap) for water, and utilizes onset dehydration and melting temperatures in combination with log P. With this model, the average absolute error for the prediction of solubility of 14 compounds was 0.32 log units.
authors.affiliation: College of Pharmacy, University of Arizona, Tucson, Arizona 85721. Electronic address: franklin@pharmacy.arizona.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Franklin
authors.affiliation: College of Pharmacy, University of Arizona, Tucson, Arizona 85721.
authors.forename: Usir S
authors.initials: US
authors.lastname: Younis
authors.affiliation: College of Pharmacy, University of Arizona, Tucson, Arizona 85721.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Myrdal
mesh_terms: D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D014867:Water / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004364:Pharmaceutical Preparations; D014867:Water
keywords: dehydration; hydrates/solvates; log P; mathematical model; solubility