Bifonazole dissolved in numerous aqueous alcohol mixtures: Solvent effect, enthalpy–entropy compensation, extended Hildebrand solubility parameter approach and preferential solvation

Abstract

The accessible mole fraction solubility of bifonazole in n-propanol/methanol/isopropanol/propylene glycol (PG) (1) + water (2) mixtures at 298.15 K was investigated in the light of molecular interactions between solvent and solute via extended Hildebrand solubility approach (EHSA). For aqueous methanol/PG systems within entire mole fraction range of methanol/PG, aqueous n-propanol system within mole fraction range of n-propanol from 0 to 0.8 and aqueous isopropanol system within mole fraction range of isopropanol from 0 to 0.7, the solute–solvent interaction energies are larger than the ones of geometric mean for regular solution, asserting that there exists some association between bifonazole and mixtures; whereas within the other composition regions for the aqueous isopropanol/n-propanol systems, the solutions consisting of bifonazole present regular behavior at several solubility points. The inverse Kirkwood–Buff integrals tool was utilized to investigate the local mole fractions of bifonazole in the solutions of alcohol (1) + water (2) in the light of the solubility. For the aqueous solutions of isopropanol/n-propanol with middle and isopropanol/n-propanol-rich mole fractions, preferential solvation of bifonazole was observed for isopropanol/n-propanol. Bifonazole was not solvated preferentially by PG/methanol in the above composition regions for aqueous PG/methanol mixtures. The solvent effect was quantitatively described by modeling the solubility change by means of the linear solvation energy relationships. The solubility parameter and dipolarity-polarizability of system descriptors presented the dominant contributions to variation of solubility values. The transfer and dissolution properties, e.g. entropy, Gibbs free energy change and enthalpy were calculated. In addition, the analysis of enthalpy–entropy compensation was performed, specifying that the variation of bifonazole solubility in the four aqueous alcohol solutions was controlled by two different mechanisms, enthalpy-driven and entropy-driven.