Solubility, solution thermodynamics, and preferential solvation of piroxicam in ethyl acetate + ethanol mixtures

Abstract

The solubility of piroxicam (PIR) in ethyl acetate (EtOAc)+ethanol (EtOH) mixtures at five temperatures from 293.15K to 313.15K was determined and the solubility data in the binary solvent mixtures at various temperatures was mathematically represented using the Jouyban–Acree model. PIR solubility in mole fraction varied from x3=1.77×10−4 in pure EtOH to x3=4.97×10−3 in pure EtOAc at 298.15K, reaching a maximum x3=5.69×10−3 in the mixture with x10=0.80. Thermodynamic quantities of dissolution and mixing of PIR were calculated by means of Gibbs and van't Hoff equations. Furthermore, preferential solvation parameters of PIR were also derived by means of the inverse Kirkwood–Buff integrals method. The preferential solvation parameter of PIR by EtOAc, δx1,3, is negative in EtOH-rich mixtures but positive in compositions from 0.36 to 0.86 in mole fraction of EtOAc. It is possible that in EtOH-rich mixtures the acidic hydrogen bonding of EtOH with the basic sites of PIR plays an important role in the drug solvation. The greater solvation by EtOAc in mixtures of similar solvent compositions could be owing mainly to polarity effects. Finally, the slight preference of PIR for EtOH in EtOAc-rich mixtures could be explained in terms of the common participation of basic sites in both solvents and/or the acidic site of EtOH with the respective functional groups of PIR.