Physicochemical Properties of a New Multicomponent Cosolvent System for the p K a Determination of Poorly Soluble Pharmaceutical Compounds

A mixture of cosolvents is described that significantly improves the solubility of most pharmaceutical compounds. The mixture consists of equal volumes of MeOH, 1,4‐dioxane, and MeCN, thereby containing polar and nonpolar solvents, and is referred to as MDM (from MeOH, dioxane, and MeCN). MDM is mixed with H 2 O until the required composition is reached. The utility of this system is that it enables analytical measurements to be performed on a wide range of compounds where measurements would be impaired in aqueous solution. We present the physicochemical characteristics of MDM/H 2 O mixtures (density, dielectric constant, p s K w ) and the principles of p K a measurement in this solvent/H 2 O mixture. We also present p K a values in H 2 O of several drug compounds determined from values measured in MDM/H 2 O mixtures.