与烟酸形成共晶改善法莫替丁溶解性研究

Improving Solubility of Famotidine by Cocrystal Synthesis with Nicotinic Acid

目的应用共晶技术提高法莫替丁的溶解性。方法选择烟酸作为共晶形成物(CCF)与法莫替丁采用挥发法制备共晶,获得的共晶采用X射线单晶衍射测定单晶结构,通过X射线粉末衍射法(PXRD)、红外光谱法(IR)、差示扫描量热法(DSC)、热重法(TGA)对共晶进行检测,同时考察了共晶的溶解性和稳定性。结果法莫替丁-烟酸共晶的不对称单元包含1个法莫替丁分子、1个烟酸分子和1个水分子,通过氢键相互连接。共晶具有特征的熔点、PXRD、IR图谱。共晶在水中的最大溶解度比法莫替丁提高了4. 2倍,并且未改变法莫替丁在人工胃液、光照、高温、高湿条件下的稳定性。结论制备的法莫替丁-烟酸共晶明显提高了法莫替丁在水中的溶解度,为应用共晶技术提高药物水溶性提供了研究基础。

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.