Measurement and mathematical modeling of ketoconazole solubility in propylene glycol + water mixtures at various temperatures

Abstract

The aim of this work was to study the solubilization behavior and thermodynamics of ketoconazole solubility in the binary mixtures of propylene glycol (PG) and water at five different temperatures ranging T = 293.2–313.2 K. Some cosolvency mathematical models including van't Hoff equation, Yalkowsky model, Jouyban-Acree model, Jouyban-Acree-van't Hoff model, modified Jouyban-Acree-van't Hoff model, the modified Wilson model, the double log-log model and the mixture response surface model were fitted to the experimental results, and the mean relative deviations (MRD%) of the back-calculated solubilities were calculated. Density of the solutions saturated with ketoconazole over the entire solvent composition and temperature range was also determined and the obtained density values were correlated/back-calculated with the Jouyban–Acree model, resulting in a very accurate calculation of the densities with MRD% of 0.1%. Moreover, apparent thermodynamic properties of ketoconazole dissolution process in the investigated mixed solvents including entropy, enthalpy and Gibbs free energy were computed using van't Hoff and Gibbs equations. Furthermore, preferential solvation analysis demonstrates that ketoconazole is preferentially solvated by water in water-rich mixtures but preferentially solvated by PG in the other mixtures.