夫西地酸晶型转化的影响因素考察  

Investigation on Factors Affecting the Crystal Transformation of Fusidic Acid

作　　者：冷凤[1] 李晓露[1] 任风芝[1] 李宁[1] 杨朝晖 LENG Feng;LI Xiaolu;REN Fengzhi;LI Ning;YANG Zhaohui(Hehei Industry Microbial Metabolic Technology Innovation Center,National Engineering Research Center of Microbial Medicine,NCPC New Drug Research&Development Co.,Ltd.,Shijiazhuang 052165;NCPC Huaheng Pharmaceutical Co.,Ltd.,Shijiazhuang 051530)

机构地区：[1]华北制药集团新药研究开发有限责任公司,微生物药物国家工程研究中心,河北省工业微生物代谢技术创新中心,河北石家庄052165 [2]河北华北制药华恒药业有限公司,河北石家庄051530

出　　处：《中国医药工业杂志》2022年第10期1504-1510,共7页Chinese Journal of Pharmaceuticals

摘　　要：采用正交试验法考察了结晶温度、抗溶剂滴加速度、结晶初始浓度以及晶种加入时机等因素对夫西地酸(1)多晶型的影响,结果表明结晶温度是影响1多晶型产生的关键因素,其次为抗溶剂滴加速度。当结晶温度为40℃,同时抗溶剂加入速度为0.1ml/min时,全部生成1无水物;结晶温度控制在20~30℃,抗溶剂加入速度控制在0.2ml/min以上时,可以得到合格的1半水合物。利用过程分析技术工具实时记录1抗溶剂结晶过程,揭示了1转晶过程中的变化。对制备的1半水合物和1无水物2种晶型进行了粉末X射线衍射和红外光谱法的表征分析,结果与文献报道一致。本研究结果可为1半水合物的规模化生产提供技术指导。The effects of the crystallization temperature,the dripping rate of antisolvent adding,the initial concentration of the crystallization and the occasion of seed crystal adding on the polymorph formation of fusidic acid(1)were investigated by the orthogonal experiment.The results showed that the crystallization temperature was the key factor affecting the polymorph formation of 1,followed by the dripping rate of antisolvent.Anhydrous 1 was formed when the antisolvent dripping rate was 0.1 ml/min and crystallized at 40℃,while 1 hemihydrate was obtained with more than 0.2 ml/min of dripping rate and 20-30℃of crystallization temperature.The crystallization process of 1 was recorded online in real time with process analysis technology tools,and the transformation process of 1 crystal forms was revealed.Powder X-ray diffractometry(PXRD)and infrared spectroscopy(IR)were applied for both anhydrate and hemihydrate products.The analysis results were consistent with the literature reports.The experimental results could provide technical guidance for the large-scale production of 1 hemihydrate.

关 键 词：夫西地酸 抗溶剂结晶 过程分析 多晶型 抗菌剂 

分 类 号：R978.19[医药卫生—药品] O742.6[医药卫生—药学]