Thermodynamic Analysis of Etoricoxib in Amphiprotic and Amphiprotic: Aprotic Solvent Mixtures at Several Temperatures

Abstract

The solubilities of etoricoxib (ETX), a COX-2 selective nonsteroidal anti-inflammatory drug, were determined in water–ethanol and ethanol–ethyl acetate mixtures at several temperatures (288.15–308.15 K). The solubility curves as a function of ethanol ratio were studied at five temperatures; they showed a single maximum located at 30% ethanol–ethyl acetate (δ1 = 19.70 MPa1/2). The measurements of the variation of inherent drug solubility with temperature were used to estimate different thermodynamic parameters, enthalpy, entropy and Gibbs energy of solution (ΔHS, ΔSS and $$\Delta G_{{{\text{hm}}}}^{{\text{S}}}$$, respectively). The apparent enthalpies of solution were nonlinear functions of the ethanol ratio in aqueous mixture. Non-linear enthalpy–entropy compensation analysis was observed indicating different dissolution mechanisms with the variation in mixture composition. The solubility enhancement is entropy driven in water-rich (0–40% v/v ethanol) and enthalpy controlled in ethanol-rich (40–100% ethanol) compositions, likely due to water structure loss around nonpolar moieties of the drug and in the ethanol rich mixtures it is the enthalpy, probably due to the better drug solvation.