Improving Solubility of Famotidine by Cocrystal Synthesis with Nicotinic Acid / 中国药学杂志

ABSTRACT

OBJECTIVE: This study was focused on obtaining and characterizing cocrystal of famotidine to improve its solubility. METHODS: A new cocrystal of famotidine with nicotinic acid(FAM-NIC) was obtained by solution evaporation. And the FAM-NIC cocrystal was characterized by single crystal X-ray diffraction, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR). In addition, the solubility and stability of cocrystal were studied. RESULTS: The asymmetric unit of FAM-NIC consisted of one molecule of famotidine, nicotinic acid, and water, and they were connected through hydrogen bonds. FAM-NIC had unique thermal, spectroscopic, X-ray diffraction, and solubility properties that differed from famotidine. Dissolution studies of the cocrystal showed a 4.2-fold increase of famotidine solubility, and FAM-NIC didn′t change the stability of famotidine in artificial gastric juice, at high humidity, at high temperature, and under illumination. CONCLUSION: The new cocrystal of famotidine with nicotinic acid obviously enhanced the solubility of famotidine.And the RESULTS can be useful for improving solubility of drugs by cocrystal synthesis.