Preparation and characterization of carbamazepine cocrystals with acidic coformers to improve their physicochemical properties

Abstract

Introduction: Solubility is one of the important physicochemical properties of pharmaceutical compounds. Salt formation is a classic approach to improve solubility of ionizable compounds. Recently, cocrystals and using of ionic liquids for solubilization of medicines has been considered as a more interesting issue in pharmaceutical sciences. Cocrystals are composed of two compounds, drug and coformer which are connected using non-covalent bonds i.e. hydrogen bond. In addition, ionic liquids which are salt in the liquid state were considered as a new approach to increase drugs’ solubility. Aims: The aims of this study are: 1) preparation of pharmaceutical cocrystal and ionic liquids of poorly soluble drugs i.e. carbamazepin and ketoconazole 2) characterization of them using different instrumental analysis methods and 3) investigation of the physicochemical properties i.e. solubility of the pharmaceutical cocrystals and ionic liquids. Methods: Carbamazepine and ketoconazole with three pharmaceutical coformers (cinnamic acid, tartaric acid and citric acid) were selected and their cocrystals (CBZ-CIN) and ionic liquids (KTZ-CA, KTZ-TA) were prepared by solvent evaporation method. The prepared pharmaceutical cocrystals and ionic liquids were characteristized by differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD) and Fourier transform infrared spectroscopy (FT-IR) methods followed by investigation of physicochemical properties such as solubility.Results: The results of different instrumental analysis methods confirm the cocrystal and ionic liquid formation. Thermodynamic solubility of CBZ-CIN cocrystal increases at higher pH levels in comparison to its intrinsic solubility. In addition, as molar ratio of coformers (TA and CA) increases, the solubility of the ionic liquids improves in comparison with non-processed KTZ's. Conclusion: Ionization of conformer in higher pH levels leads to an increase in CBZ-CIN solubility. Ionic hydrogen bond formation between imidozalic functional group of KTZ and the carboxyl group of polyprotic organic acids, i.e. CA and TA can give oligomeric ILs.