Dissolution Thermodynamics and Preferential Solvation of Ketoconazole in Some {Ethanol (1) + Water (2)} Mixtures Publisher



Jouyban A^{1, 2} ; Martinez F⁴ Show Affiliations
Source: Journal of Molecular Liquids Published:2020

Abstract

In this research, the equilibrium mole fraction solubility of ketoconazole in some aqueous-ethanolic mixtures was calculated from previously measured solubility data reported in molarity scale at temperatures from 298.2 to 313.2 K. Experimental mole fraction solubility values were adequately correlated with the Jouyban-Acree and Jouyban-Acree-van't Hoff models. The respective apparent thermodynamic functions (Gibbs energy, enthalpy, and entropy of the dissolution processes) were computed using the van't Hoff and Gibbs equations. The enthalpy–entropy relationship for ketoconazole was non-linear in the plot of enthalpy vs. Gibbs energy of solution with negative slope in the composition region 0.00 ≤ w1 ≤ 0.20 but positive slope in the region 0.20 ≤ w1 ≤ 0.70. Beyond this composition, the behavior is more complex. Therefore, the driving mechanism for ketoconazole dissolution process is the entropy in water-rich mixtures and the enthalpy in mixtures 0.20 ≤ w1 ≤ 0.70. In addition, the inverse Kirkwood-Buff integrals were used to investigate the preferential solvation of ketoconazole which is preferentially solvated by water molecules in water-rich and also in ethanol-rich mixtures but preferentially solvated by ethanol molecules in mixtures 0.24 ≤ x1 ≤ 0.75. Dissolution thermodynamics and preferential solvation computations were carried out employing whole experimental solubility data points and the simulated data using a minimum number of seven data points as training set, in which there were no significant differences in the obtained numerical values except for enthalpy-entropy compensation data. © 2020 Elsevier B.V.