Solubilization and determination of solution thermodynamic properties of itraconazole in different solvents at different temperatures

The solubility of itraconazole (ITRA) in thirteen pure solvents including water, dimethyl sulphoxide, acetonitrile, methanol, 1,4-butanediol, ethanol, isopropyl alcohol, n-butanol, octanol, ethyl acetate, toluene, benzene, 1,4-dioxane were estimated at the temperatures ranging from 293.15 K to 318.15 K under atmospheric pressure (0.1 MPa). The results reflected that the solubility of ITRA was a function of temperature and was increased with a rise in temperature in each solvent. Moreover, the solubility in polar solvents was less and found to be increased in non-polar solvents. Furthermore, the results of solubilization were correlated by the Van't Hoff equation, the modified Apelblat equation, the Buchowski - Ksiazaczak λh equation, and the polynomial empirical equation. The polynomial empirical equation proved to be more accurate and suitable for the correlation of solubilities of ITRA in studied solvents at various temperatures. Besides, theoretical ideal solubilities, activity coefficients, and thermodynamic properties of the solution process including standard molar enthalpy, entropy, Gibbs free energy, and excess enthalpy were calculated from the experimental solubility data. These thermodynamic parameters indicated that the solubilization process was not spontaneous, endothermic, and enthalpy driven. Such thermodynamic based solubility data of ITRA will be of immense help in solubilization, synthesis, process development, preformualtion, and dosage form development in pharmaceuticals.