Thermodynamic Analysis for the Solubility of Allopurinol in Aqueous and Non-aqueous Mixtures at Various Temperatures

Abstract

The solubility of allopurinol was measured at several temperatures (15–35 ºC) in ethanol–water, ethanol–ethyl acetate, and ethyl acetate–hexane mixtures. The mole fraction solubility shows two solubility maxima against the co-solvent (ethanol) ratio (70 % ethanol–water and 100 % ethyl acetate) at each of the five temperatures studied. The authors correlated the solubility data in binary solvent mixtures at various temperatures using a modified version of the Jouyban–Acree model. The respective apparent thermodynamic functions Gibbs energy, enthalpy, and entropy of solution were obtained from the solubility data through the van’t Hoff equations. The apparent enthalpies of solution are endothermic and display a maximum at 20 % ethanol in water, as ethanol is added to water, the entropy of the system increases. In the non-aqueous mixture (ethanol–ethyl acetate), enthalpy is the driving force throughout the whole solvent composition. An enthalpy–entropy compensation analysis confirms a non-linear enthalpy–entropy relationship in plots of enthalpy vs. Gibbs energy of solution, i.e., two different mechanisms involved in the solubility enhancement. An inverse Kirkwood–Buff integral analysis of the preferential solvation indicated that in ethanol-rich mixtures, the drug is preferentially solvated by water, and it is acting mainly as a Lewis base in front to water.