Preparation, Characterization and Solubility Study of Ethenzamide-oxalic Acid Cocrystal

OBJECTIVE To prepare ethenzamide-oxalic acid cocrystal and study the solubility of cocrystal in phosphate buffer saline(PBS) and simulated gastric juice(SGF). METHODS By using solution crystallization method, ethenzamide and oxalic acid were dissolved in ethyl acetate, and the solution was slowly cooled to room temperature, the ethenzamide-oxalic acid cocrystal was obtained through crystallization, filtration and drying. The structure of cocrystal was characterized by single crystal X-ray diffraction(SCXRD), powder X-ray diffraction(PXRD), differential scanning calorimeter(DSC), then solubility was tested. RESULTS The cocrystal was finally formed with ethenzamide and oxalic acid by the stoichiometric ratio of 2:1. The solubilities for studied cocrystal in PBS and SGF appeared to be approximately 2.0 and 2.5 times-fold higher than ethenzamide. CONCLUSION The study provides a theoretical basis for improving the solubility of drugs by forming the cocrystal of insoluble drugs with oxalic acid, which is generally recognized as safe additives.