The solubility of ketoconazole in binary carbitol + water mixtures at T = (293.2–313.2) K

Abstract

The solid-liquid equilibrium of ternary {ketoconazole + carbitol + water} systems was studied by a shake-flask technique at T = (293.2–313.2) K and atmospheric pressure. The temperature and solvent composition dependency models of Jouyban-Acree, Jouyban-Acree-van't Hoff, NRTL, UNIQUAC and Wilson as well as solvent composition dependency models of combined nearly ideal binary solvent/Redlich-Kister (CNIBS/R-K) and modified Wilson were utilized for modeling the experimental solubility data. To predict the solubility data, Yalkowsky and extended Yalkowsky models were utilized. It was observed that the solubility of ketoconazole was increased with the enhancement in temperature and concentration of carbitol. According to the % ARD values, order of performance of the models with temperature and solvent composition dependencies are Jouyban-Acree-van't Hoff > NRTL > Jouyban-Acree > UNIQUAC > Wilson. The % ARD values indicate that in comparison between the models with solvent composition dependency, CNIBS/R–K model has a better consistency with the experimental data. Further, the computed thermodynamic properties of dissolution for ketoconazole in aqueous carbitol solutions suggest that except in neat water, enthalpy has the main contribution to standard Gibbs free energies of dissolution. Finally, preferential solvation analysis based on the inverse Kirkwood-Buff integrals demonstrates that ketoconazole is preferentially solvated by water in water-rich mixtures but preferentially solvated by carbitol in mixtures of 0.12 < x1 < 1.00.