拉帕替尼纳米晶的制备与表征  

Preparation and Characterization of Lapatinib Nanocrystals

作　　者：张朵朵 冯菊红[1,2] 周洁 刘云[1,2] 汪诗雨[1,2] 沈宇寒[1,2] 胡学雷 ZHANG Duoduo;FENG Juhong;ZHOU Jie;LIU Yun;WANG Shiyu;SHEN Yuhan;HU Xuelei(School of Chemical Engineering and Pharmacy,Wuhan Institute of Technology,Wuhan 430074,China;Key Laboratory of Green Chemical Process of Ministry of Education,Wuhan 430074,China)

机构地区：[1]武汉工程大学化工与制药学院,湖北武汉430074 [2]绿色化工过程教育部重点实验室,湖北武汉430074

出　　处：《化学与生物工程》2023年第4期29-34,共6页Chemistry & Bioengineering

基　　金：湖北省自然科学基金重点项目(2011CDA048)。

摘　　要：采用介质研磨法制备了拉帕替尼纳米晶(LPT-NC),以粒径和多分散指数(PDI)为评价指标,优化了制备工艺;并通过扫描电镜(SEM)、X-射线粉末衍射仪(XRPD)、差式扫描量热仪(DSC)等对LPT-NC进行了表征。结果表明,以15%羟丙纤维素为稳定剂、5%甘露醇为冻干保护剂,在LPT质量浓度为10%、氧化锆珠粒径为0.3 mm、氧化锆珠用量为9 g、研磨时间为2.0 h的最优条件下,制备的LPT-NC相较于LPT原料药并没有发生晶型的改变;平均粒径为(220.35±3.75)nm、平均PDI为0.196±0.015;20 min内达到溶出平衡,累积溶出度为90.12%,是原料药的9倍左右,且放置90 d后仍具有良好的体外溶出特性。为提高抗癌药LPT的水溶性和溶出度研究提供了科学依据。We prepared Lapatinib nanocrystals(LPT-NC)by a medium grinding method,and optimized the preparation process by using particle size and polydispersity index(PDI)as evaluation indexes.Moreover,we characterized the structure of LPT-NC by scanning electron microscope(SEM),X-ray powder diffractometer(XRPD),differential scanning calorimeter(DSC),etc.The results show that the crystal form of the prepared LPT-NC has no change compared with the LPT active pharmaceutical ingredient(API)by using 15%hydroxypropyl cellulose(HPC)as a stabilizer and 5%mannitol as a freeze-drying protective agent under the optimal conditions as follows:the mass concentration of LPT is 10%,the particle size of zirconia is 0.3 mm,the amount of zirconia is 9 g,and the grinding time is 2.0 h.The average particle size of LPT-NC is(220.35±3.75)nm,and the average PDI is 0.196±0.015.The prepared LPT-NC reaches dissolution equilibrium within 20 min,and the cumulative dissolution is 90.12%,which is about 9 times of API,and still has good dissolving characteristic in vitro after 90 d.The study provides a scientific basis for improving the water solubility and dissolution of anticancer drug LPT.

关 键 词：拉帕替尼 纳米晶 制备工艺 表征 累积溶出度 

分 类 号：TQ463[化学工程—制药化工]