芒柄花素-4,4’-联吡啶共晶的制备表征及溶解性能  

Preparation,Characterization and Properties of Solubility of Formononetin-4,4'-Bipyridine Cocrystal

作　　者：房政钰 王雪[1] 邢逞[1] 龚宁波[1] 吕扬[1] FANG Zhengyu;WANG Xue;XING Cheng;GONG Ningbo;LYU Yang(Beijing Key Laboratory of Polymorphic Drugs,Institute of Materia Medica,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100050,China)

机构地区：[1]北京协和医学院、中国医学科学院药物研究所晶型药物研究北京市重点实验室,北京100050

出　　处：《医药导报》2022年第5期616-620,共5页Herald of Medicine

基　　金：国家重点研发计划(2016YFC1000900);中国医学科学院医学与健康科技创新工程项目(2017-I2M-1-010);国家科技重大专项-重大新药创制(2018ZX09711001-001,2018ZX09711001-010)。

摘　　要：目的采用共晶技术改善芒柄花素水溶性。方法采用悬浮液法和加液研磨法制备一种新的芒柄花素-4,4’-联吡啶共晶,利用磁共振波谱法(NMR)、粉末X射线衍射法(PXRD)、红外光谱法(IR)、差示扫描量热法(DSC)对共晶进行表征。使用高效液相色谱法考察了共晶的溶解性能,采用PXRD进行稳定性评价。结果采用悬浮液法和加液研磨法可以制备纯度较高的芒柄花素-4,4’-联吡啶共晶,共晶的平衡溶解度相比原料药提高了2.61倍,且共晶在高温[(60±1)℃]、高湿[(90±5)%,25℃]和光照[(4500±500)lx,25℃]下均保持稳定。结论芒柄花素-4,4’-联吡啶共晶稳定性良好,可显著提高原料药的溶解性。Objective To improve solubility of formononetin by cocrystal technology.Methods A new cocrystal of formononetin with 4,4'-bipyridine was prepared by the solvent suspension and liquid assisted grinding.The cocrystal was characterized by nuclear magnetic resonance spectroscopy(NMR),powder X-ray diffraction(PXRD),infrared spectroscopy(IR),and differential scanning calorimetry(DSC).The solubility of the cocrystal was investigated by high performance liquid chromatography,and the stability was evaluated by PXRD.Results The formononetin-4,4'-bipyridine cocrystal with higher purity can be prepared by solvent suspension and liquid assisted grinding.The equilibrium solubility of formononetin-4,4'-bipyridine cocrystal was increased approximately by 2.61 folds compared to raw material.The cocrystal was stable under temperature[(60±1)℃],humidity[(90±5)%,25℃],and light[(4500±500)lx,25℃].Conclusion Formononetin-4,4'-bipyridine cocrystal with good stability can significantly improve the solubility of the bulk drug.

关 键 词：芒柄花素 4 4’-联吡啶 共晶 制备 表征 溶解度 

分 类 号：R979.1[医药卫生—药品] TQ460.6[医药卫生—药学]