Dissolution behavior and preferential solvation of diacerein in mixtures of (ethyl acetate/acetonitrile + ethanol) at several temperatures

Abstract

Because the chemical structure of diacerein is plane structure, the solubility of diacerein is poor, and most of the products crystallized by solvent contain solvate, so it is difficult to get a large amount of diacerein without solvate. The present work demonstrates cosolvent as a successful technique to improve the dissolution property of diacerein. The solid liquid equilibrium phase diagram of diacerein in mixtures of (ethyl acetate/acetonitrile + ethanol) within the temperature range from (273.15 to 313.15) K was studied and represented using Jouyban-Acree model. The solubility profile of diacerein in two mixtures increased at first and then decreased with the increasing mass fraction of ethyl acetate/acetonitrile. In (ethyl acetate + ethanol) and (acetonitrile + ethanol) mixtures, the minimum mole solubility was obtained in pure ethanol, 5.085 × 10−5, and the maximum data in (ethyl acetate + ethanol) mixtures was 2.568 × 10−4 at the composition of w(ethyl acetate) = 0.8 (mass fraction), and 1.727 × 10−4 for (acetonitrile + ethanol) systems at w(acetonitrile) = 0.6, respectively. Preferential solvation parameters (δx1,3) of diacerein in two mixtures were evaluated by using the inverse Kirkwood-Buff integrals method, and it was all negative in ethanol-rich mixtures but positive at the mole compositions of ethyl acetate from 0.37 to 0.61, and with the range from 0.53 to 0.61 for acetonitrile. However, it should be noted that the positive preferential solvation parameters in acetonitrile + ethanol mixtures are lower than 0.01, near 0.002, and thus, a consequence of uncertainties propagation in IKBI calculations must be taken into account here. Moreover, the corresponding relative average deviations (RAD) of solubility correlation are 4.96% and 5.74%, respectively. The values of ΔHsolo were from 22.68 to 36.45 kJ·mol−1. The analysis of apparent thermodynamic properties shows that the dissolution process in all investigated solvent mixtures is an endothermic and entropy driven process.