基于热分析技术的替格瑞洛晶型Ⅱ热性能研究  

Study on thermal properties of ticagrelor form Ⅱ based on thermal analysis technology

作　　者：周新波 金志平 任燕 陈林深 祝占根 胡秀荣[2] ZHOU Xin-bo;JIN Zhi-ping;REN Yan;CHEN Lin-shen;ZHU Zhan-gen;HU Xiu-rong(Zhejiang Jingxin Pharmaceutical Co.,Ltd.,Xinchang 312500,China;Chemistry Department,Zhejiang University,Hangzhou 310028,China)

机构地区：[1]浙江京新药业股份有限公司,新昌312500 [2]浙江大学化学系,杭州310028

出　　处：《药物分析杂志》2023年第9期1461-1467,共7页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:对替格瑞洛晶型Ⅱ的热性能进行分析与研究。方法:通过差示扫描量热法和热台显微镜分析替格瑞洛晶型Ⅱ的热性能,并结合粉末X射线衍射法和光学显微镜分析替格瑞洛晶型Ⅱ的晶型及晶习特征与热性能的关系。结果:替格瑞洛晶型Ⅱ存在不同长径比的特征晶习,在粉末X射线衍射图上表现为特征峰相对强度的变化。替格瑞洛晶型Ⅱ在熔融过程中存在熔融转晶现象,晶习特征、粒径大小及分布,以及差示扫描量热仪的升温速率对其熔融转晶程度有较大影响。在粉末X射线衍射图谱等其它表征结果证实为替格瑞洛晶型Ⅱ的情况下,其差示扫描量热图谱上出现双峰现象为熔融转晶引起而非混晶造成。结论:通过对替格瑞洛晶型Ⅱ的热性能研究,为其差示扫描量热图谱有的呈现双峰有的呈现单峰的现象提供了合理的解释,为替格瑞洛原料药的质量控制提供更多的信息。Objective:To study the thermal properties of ticagrelor formⅡ.Methods:Thermal properties of ticagrelor formⅡwas analyzed by differential scanning calorimetry and hot stage microscopy.Combined with powder X-ray diffraction and optical microscopy,the relationship between the crystal form,crystal habit and thermal properties of ticagrelor formⅡwas analyzed.Results:Ticagrelor formⅡhad needle-like crystal habit with different aspect ratios,which were manifested as the changes of relative intensities of characteristic peaks on the powder X-ray diffraction pattern.There was a melting transition phenomenon of ticagrelor formⅡin the heating process.Crystal habit,particle size,as well as the heating rate of differential scanning calorimeter had a great influence on the degree of melting transition phenomenon.The double peaks in DSC spectrum could be caused by polymorphic transformation rather than mixed polymorphic crystal when PXRD and other characterization results showed that it was pure ticagrelor formⅡ.Conclusion:Through the study of the thermal properties of ticagrelor formⅡ,it provides a reasonable explanation for the phenomenon that some DSC patterns of the same drug substance with the same crystal form showed double peaks and some showed single peaks.This study provides more information for the quality control of ticagrelor.

关 键 词：替格瑞洛 晶型转变 热性能 冷结晶 差示扫描量热法 粉末X射线衍射法 

分 类 号：R917[医药卫生—药物分析学]