Physicochemical characterization of a new cocrystal of ketoconazole

Abstract

This study presents characterization and physicochemical properties of a new cocrystal of ketoconazole (KTZ). Cocrystal formation of KTZ with two different coformers, i.e. nicotinamide and 4-amino benzoic acid (PABA) was evaluated using the thermal approach and the developed KTZ cocrystal with PABA was prepared through solvent evaporation method. The synthesized cocrystal was characterized by differential scanning calorimetry, powder X-ray diffraction and Fourier transform infrared spectroscopy. The dissolution profile and apparent solubility of KTZ-PABA cocrystal were determined in 0.1 M HCl (pH similar to 1), acetate buffer solution at pH 4.2, water and phosphate buffer solution at pH 6.8 to simulate physiological conditions and compare with those of KTZ. Dissolution profile and apparent solubility of the cocrystal have been increased in a non-acidic condition because of higher solubility of the coformer. Thermodynamic solubility of the cocrystal was calculated using eutectic concentrations of both components and it gave information about stability and solubility of cocrystal in solution. These findings in this study showed that the higher coformer solubility than the drug leads to the cocrystal being less stable but more soluble. Solubility of coformer and solution stability of cocrystal are two important parameters in cocrystal solubility. (C) 2014 Elsevier B.V. All rights reserved.