羟基喜树碱纳米晶制备及药剂学性质研究  

Preparation and pharmaceutical properties of hydroxycamptothecin nanocrystals

作　　者：赵鹏飞 李慧霞 甘丹 陈小飞 赵红天 陈明杨 戎欣玉[1,2] ZHAO Peng-fei;LI Hui-xia;GAN-Dan;CHEN Xiao-fei;ZHAO Hong-tian;CHEN Ming-yang;RONG Xin-yu(Hebei University of Science&Technology,College of Chemical&Pharmaceutical Engineering,Hebei Shijiazhuang 050018,China;Hebei Pharmaceutical Chemical Engineering Technology Research Center,Hebei Shijiazhuang 050018,China)

机构地区：[1]河北科技大学化学与制药工程学院,河北石家庄050018 [2]河北省药物化工工程技术研究中心,河北石家庄050018

出　　处：《中国医院药学杂志》2021年第23期2401-2405,2446,共6页Chinese Journal of Hospital Pharmacy

基　　金：河北省自然科学基金资助项目(编号:H2014208151)。

摘　　要：目的:制备羟基喜树碱纳米晶体并进行药剂学性质研究。方法:采用湿法介质研磨制备羟基喜树碱纳米晶体;用马尔文激光粒度仪测定羟基喜树碱纳米晶体的平均粒径和多分散指数(PDI);用扫描电镜观察晶体形态;用X-射线粉末衍射法(XRPD)、差示扫描量热法(DSC)及傅里叶红外光谱法(FTIR)分析晶型和化学结构有无变化;用透析袋法测定纳米晶体的溶出度。结果:制备的羟基喜树碱纳米晶体平均粒径为104 nm,PDI值为0.215;羟基喜树碱纳米化前后晶型和化学结构没有发生明显的改变;纳米化后的药物溶出度明显提高,药物溶出参数T_(50)和T_(D)(药物溶出50.0%和63.2%所需时间)显著减少。结论:湿法介质研磨制备羟基喜树碱纳米晶体方法可行,平均粒径较小且分布较均匀;研磨后的羟基喜树碱晶型未被破坏,仍为结晶态;制成的羟基喜树碱纳米晶体溶出性能明显改善。OBJECTIVE To prepare hydroxycamptothecin nanocrystals and examine their pharmaceutical properties.METHODS Hydroxycamptothecin nanocrystals were prepared by wet grinding method.The average particle size and polydispersity index(PDI)of hydroxycamptothecin nanocrystals were determined by Malvern laser particle size analyzer;Crystal morphology was observed by scanning electron microscope(SEM);X-ray powder diffraction(XRPD),differential scanning calorimetry(DSC)and Fourier transform infrared spectroscopy(FTIR)were utilized for analyzing the changes of crystal form and chemical structure.The dissolution of nanocrystals was determined by dialysis bag method.RESULTS The average particle size of prepared hydroxycamptothecin nanocrystals was 104 nm with a PDI value of 0.215.Crystal form or chemical structure of hydroxycamptothecin showed no marked change before and after nanocrystallization.After nanocrystallization,dissolution rate spiked sharply and drug dissolution parameters T_(50) and T_(D)(time required for drug dissolution of 50.0%and 63.2%)declined markedly.CONCLUSION With a smaller average particle size and a more uniform distribution,it is feasible to prepare hydroxycamptothecin nanocrystals by wet medium grinding method.Crystal form of hydroxycamptothecin remains intact after grinding.The dissolution properties of prepared hydroxycamptothecin nanocrystals have obviously improved.

关 键 词：羟基喜树碱 纳米晶体 介质研磨 药剂学性质 溶出度 

分 类 号：R944[医药卫生—药剂学]