克唑替尼固体分散体的制备及体外溶出度研究  

Preparation and in vitro Dissolution of Crizotinib Solid Dispersion

作　　者：汪诗雨 周洁 刘云[1,2] 冯菊红[1,2] 葛燕丽[1,2] 胡学雷[1,2] WANG Shiyu;ZHOU Jie;LIU Yun;FENG Juhong;GE Yanli;HU Xuelei(School of Chemical Engineering and Pharmacy,Wuhan Institute of Technology,Wuhan 430205,China;Key Laboratory for Green Chemical Process of Ministry of Education,Wuhan 430205,China)

机构地区：[1]武汉工程大学化工与制药学院,湖北武汉430205 [2]绿色化工过程教育部重点实验室,湖北武汉430205

出　　处：《化学与生物工程》2024年第5期51-55,共5页Chemistry & Bioengineering

基　　金：湖北省自然科学基金重点项目(2011CDA048)。

摘　　要：为了提高克唑替尼的溶解度进而改善其生物利用度,采用冷冻干燥法制备了克唑替尼固体分散体,以体外累积溶出度为评价指标,对其制备工艺进行了优化;并通过傅立叶变换红外光谱仪(FTIR)、X-射线衍射仪(XRD)、扫描电子显微镜(SEM)和差示扫描量热仪(DSC)对克唑替尼固体分散体进行了表征。结果表明,在克唑替尼与载体羟丙基甲基纤维素(HPMC)的质量比为1∶3、反应溶剂为叔丁醇、反应温度为50℃、反应时间为30 min的最佳条件下,克唑替尼固体分散体的溶出效果最佳,60 min体外累积溶出度达到93.98%,远高于克唑替尼原料药(10.96%);克唑替尼以无定形态高度分散于载体HPMC中。In order to increase the solubility of Crizotinib and thereby improve its bioavailability,we prepared Crizotinib solid dispersion by a freeze-drying method.Moreover,taking in vitro cumulative dissolution as an evaluation index,we optimized the preparation process of Crizotinib solid dispersion.Furthermore,we characterized Crizotinib solid dispersion by FTIR,XRD,SEM,and DSC.The results show that,when the mass ratio of Crizotinib to carrier hydroxypropyl methylcellulose(HPMC)is 1∶3,the reaction solvent is tert-butanol,the reaction temperature is 50℃,and the reaction time is 30 min,the dissolution effect of Crizotinib solid dispersion is the best,and the in vitro cumulative dissolution can reach 93.98%within 60 min,which is much higher than that of Crizotinib active pharmaceutical ingredient(API)(10.96%).Crizotinib is highly dispersed in the carrier HPMC in an amorphous form.

关 键 词：克唑替尼 固体分散体 冷冻干燥法 体外累积溶出度 

分 类 号：TQ463[化学工程—制药化工] R979.1[医药卫生—药品]