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

Abstract

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 H2O 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/H2O mixtures (density, dielectric constant, psKw) and the principles of pKa measurement in this solvent/H2O mixture. We also present pKa values in H2O of several drug compounds determined from values measured in MDM/H2O mixtures.

Experimental and Theoretical Studies of Oxalic Acid Dissociation in Water-Ethanol Solvents

“…In relations (4) and (5) [18], [19] which characterizes the average of approach distant of the solvated ions supposed to be 5 . and were computed using equations (6) and (7).…”

pKa-critical Interpretations of Solubility–pH Profiles: PG 300995 and NSC-639829 Case Studies

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