基于热分析技术的白桦脂醇多晶型发现与表征  

Discovery and Characterization of Betulin Polymorphs Based on Thermal Analysis Technology

作　　者：刘琪文 陈婷[1] 安琪 杨世颖[1] 杨德智[1] 吕扬[1] 杜冠华[2] LIU Qiwen;CHEN Ting;AN Qi;YANG Shiying;YANG Dezhi;LYU Yang;DU Guanhua(Beijing Key Laboratory of Polymorphs Drugs Research,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;Beijing Key Laboratory of Drug Target and Screening Research,Institute of Materia Medica,Chinese Academy of Medical Sciences and 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 [2]北京协和医学院、中国医学科学院药物研究所药物靶点研究与新药筛选北京市重点实验室,北京100050

出　　处：《医药导报》2022年第5期637-641,共5页Herald of Medicine

基　　金：中国医学科学院医学与健康科技创新工程(2020-I2M-1-003);中国医学科学院中央级公益性科研院所基本科研业务费资助项目(2021-RW350-001)。

摘　　要：目的基于白桦脂醇的热力学性质,探讨白桦脂醇新晶型及确定稳定性好、溶解性高的优势药用晶型。方法对白桦脂醇晶A型热分析的特征图谱进行分析,发现白桦脂醇3种新晶型,采用差示扫描量热法(DSC)、热重法(TG)、粉末X射线衍射法(PXRD)对晶型进行结构表征。采用PXRD进行稳定性评价,采用高效液相色谱法(HPLC)考察晶型的溶解性能。结果利用相变温度发现了白桦脂醇的3种新晶型,分别为晶B型、晶C型和晶D型。通过稳定性和溶解度评价确定了其优势药用晶型为晶D型(无定型),其在0.5%十二烷基硫酸钠(SDS)溶液中溶解性最好,且在高温[(60±1)℃]、高湿[(90±5)%,25℃]和光照[(4500±500)lx,25℃]条件下稳定。结论相比于多晶型研究常用的筛选方法,该研究发现白桦脂醇不同晶型之间的相变规律,为白桦脂醇多晶型的发现和深入研究提供了参考方法,具有简便、快捷的优点。Objective Based on the thermodynamic properties of betulin,new crystal forms of betulin were discovered and crystal form of dominant drug with good stability and improved solubility was determined.Methods Three new crystal forms of betulin were found by analyzing the characteristic profiles of the thermal analysis of betulin form A.The crystalline forms were characterized through differential scanning calorimetry(DSC),thermogravimetry(TG),and powder X-ray diffraction(PXRD).PXRD was used to evaluate the stability,and high performance liquid chromatography(HPLC)was used to investigate the solubility properties of the crystal forms.Results Three new crystal forms combined with phase change temperatures,namely form B,form C and form D were discovered.The dominant drug crystal form of Betulin was determined to be form D(amorphous)by stability and solubility evaluation,which was best soluble in 0.5%sodium dodecyl sulfate(SDS)solution and stable at high temperature[(60±1)℃],high humidity[(90±5)%,25℃]and light[(4500±500)lx,25℃]conditions.Conclusion Compared with the conventional screening methods in polymorphic research,this study finds the law of phase transitions between different crystal forms of betulin,which provides a reference method for the discovery of polymorphs,a reference method for the discovery and in-depth study of betulin's polymorphs,and has the advantages of simplicity and speed.

关 键 词：白桦脂醇 多晶型 热分析 表征 优势药物晶型 

分 类 号：R917[医药卫生—药物分析学] TQ460.6[医药卫生—药学]