Solubility of ketoconazole in the binary mixtures of 2-propanol and water at different temperatures

Abstract

In the present study, the solubility of ketoconazole is measured by a shake – flask method in the binary solvent mixtures of 2-propanol + water at different temperatures. The experimental solubility data are correlated/back-calculated by some cosolvency models i.e. van't Hoff, Yalkowsky, Jouyban-Acree, Jouyban-Acree-van't Hoff, the mixture response surface and the modified Wilson models. Moreover, the density of ketoconazole saturated solutions is fitted by Jouyban-Acree model and the obtained equation is reported. The accuracy of these models is investigated by calculation of the corresponding MRD%. The apparent thermodynamic parameters including dissolution standard enthalpy change (ΔH∘), standard entropy change (ΔS∘), Gibbs free energy change (ΔG∘) for ketoconazole dissolution are calculated by using van't Hoff and Gibbs equations. Moreover, the preferential solvation analysis demonstrates that ketoconazole is preferentially solvated by water in water-rich and in 2-propanol-rich mixtures, but preferentially solvated by 2-propanol in mixtures of composition 0.19 < x1 < 0.58.