Preferential solvation and solute-solvent interactions of posaconazole in mixtures of (ethyl acetate + ethanol/isopropanol) at several temperatures

Abstract

In this work, the dissolution process of stable crystalline form I in mixtures of (ethyl acetate + ethanol/isopropanol) at several temperatures was studied and represented by using Jouyban-Acree model, which was considered to be useful in the development of a pharmaceutical product. The influence of solvent properties of mixed solvents on the solubility of posaconazole was analyzed by KAT-LSER method. The solubility of posaconazole in mixture of ethyl acetate + isopropanol increased monotonically with the increasing mass fraction of ethyl acetate. However, it increased firstly and then decreased with the rising mass fraction of ethyl acetate in ethyl acetate + ethanol, and the maximum mole solubility was 4.871 × 10−4 when the mass fraction of ethyl acetate is w = 0.50 at T = 313.15 K. The co-solvency phenomenon was investigated by solubility parameters method. More importantly, preferential solvation parameters (δx1,3) of posaconazole in two mixtures were calculated by using the inverse Kirkwood-Buff integrals method, and it was all negative in ethyl acetate + ethanol system and ethanol-rich mixture in ethyl acetate + isopropanol, but positive at the mole compositions of ethyl acetate from 0.44 to 1.0 in ethyl acetate + isopropanol. Furthermore, some apparent thermodynamic properties including apparent molar standard dissolution enthalpy (ΔHsolo), apparent molar standard Gibbs energy (ΔGsolo), apparent molar standard dissolution entropy (ΔSsolo), the relative contributions by enthalpy (ζH) and by entropy (ζTS) toward to Gibbs energy were calculated by the van’t Hoff equation. Consequently, the experimental solubility and thermodynamic parameters could be used as the reference for simulation in the purification and separation of posaconazole.