Solubility of ketoconazole in N-methyl-2-pyrrolidone + water mixtures at T = (293.2 to 313.2) K

The aim of this investigation was to study the solubility behavior of ketoconazole in the binary mixed solvents of N-methyl-2-pyrrolidone (NMP) and water within the temperature range of 293.2–313.2 K and develop mathematical models using five cosolvency models; i.e. van't Hoff equation, Yalkowsky model, Jouyban-Acree model, Jouyban-Acree-van't Hoff model and modified Wilson model. In addition, density of the solutions saturated with ketoconazole in various solvent compositions and temperatures was measured and the results were correlated according to the Jouyban–Acree model. Moreover, apparent thermodynamic quantities of ketoconazole dissolution process in the NMP/water mixtures, including entropy, enthalpy and Gibbs free energy were computed using van't Hoff and Gibbs equations. The modeling showed that the mean relative deviation (MRD%) of the back-calculated solubility data using the above mentioned models were 2.9%, 55.4%, 13.6%, 8.6% and 21.8% respectively.