Ketoconazole solubility in aqueous binary mixtures of 1‑propanol at various temperatures

Abstract

The aim of this work is to have a brief overview on various solubilization methods reported for ketoconazole and using a commonly used method, i.e. cosolvency for enhancement of ketoconazole in binary mixtures of 1‑propanol and water at different temperatures. The generated data are correlated with eight cosolvency mathematical models including the van't Hoff, the double log-log, the mixture response surface, Yalkowsky, Jouyban-Acree, Jouyban-Acree-van't Hoff, modified Jouyban-Acree-van't Hoff, and the modified Wilson models. The mean relative deviations (MRD%) of the back-calculated solubility for each investigated models are calculated as an accuracy criterion. Density of the ketoconazole saturated solutions as another physico-chemical properties is also fitted by the Jouyban-Acree model. Moreover, standard enthalpy, entropy and Gibbs free energy change for ketoconazole dissolution process were obtained by using van't Hoff and Gibbs equations. 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 1‑propanol in mixtures of 0.19 < x1 < 1.00.