Solubility of fluconazole in (ethanol + water) mixtures: Determination, correlation, dissolution thermodynamics and preferential solvation

Abstract In this research, the equilibrium mole fraction solubility of fluconazole (FLC) in some aqueous-ethanolic mixtures was determined at seven temperatures from (293.15 to 323.15) K. The respective apparent thermodynamic functions (Gibbs energy, enthalpy, and entropy) for the dissolution, mixing and solvation processes were computed using the van’t Hoff and Gibbs equations. The enthalpy–entropy relationship for FLC was non-linear in the plot of enthalpy vs. Gibbs energy of solution with negative slope in the composition regions of 0.00 ≤ w1 ≤ 0.40 and 0.70 ≤ w1 ≤ 1.00. Thus, the driving mechanism for FLC transfer processes in water-rich mixtures is the entropy. In addition, by means of the inverse Kirkwood-Buff integrals is observed that FLC is preferentially solvated by water molecules in water-rich mixtures but preferentially solvated by ethanol molecules in the mixtures of 0.23