不同方法制备羟基喜树碱纳米晶体混悬液的工艺比较与质量评价

Process Comparison and Quality Evaluation of Hydroxycamptothecin Nanoscale Suspension Prepared by Different Methods

目的本文采用两种技术制备羟基喜树碱纳米晶体混悬液,比较两者工艺差异,并对不同方法制得的纳米晶体混悬液进行质量评价,用以筛选出合适的制备工艺。方法采用湿磨法和高压均质法制备羟基喜树碱纳米晶体混悬液,比较两者工艺的时间、仪器清洗、易损耗材等,测定两种方法的纳米晶体粒径大小及多分散系数、外观形态,分别对其含量及体外释放度进行质量评价。结果高压均质法制得的纳米晶体混悬液平均粒径为(350.5±20.6)nm,PDI为(0.19±0.08);湿磨法制得的纳米晶体混悬液平均粒径为(380.2±25.3)nm,PDI为(0.29±0.05)。扫描电镜下羟基喜树碱纳米晶体呈长棒状;高压均质法制得的主药含量损失率低于湿磨法。在0.2%SDS-PBS(p H=7.4)介质中释放速率无显著差异(P>0.05)。结论本文最终采用高压均质法制备羟基喜树碱纳米晶体混悬液,制得的纳米晶体混悬液粒径分布均匀,工艺简单,质量可控,易于实现工艺放大。

Objective In this study,two kinds of technology were used to prepare hydroxycamptothecin nanocrystal suspension.Their differences were compared,and the quality of nanocrystal suspensions prepared by different methods were evaluated,so as to screen out the appropriate preparation process. Methods The hydroxycamptothecin nanocrystal suspensions were prepared by wet milling and high pressure homogenization.The time of the two processes,instrument cleaning,and lossy materials were compared. The nanocrystal particle sizes,polydispersity,and the appearance of the two methods were determined.The quality of their content and in vitro release rate were also evaluated respectively. Results The average particle size of nanocrystal suspension obtained by high-pressure homogenization method was（ 350.5±20.6） nm,and PDI was（ 0.19±0.08）.The average particle size of nanocrystalline suspension prepared by wet grinding was（ 380.2±25.3） nm and PDI was（ 0.29±0.05）.Under scanning electron microscope,the hydroxycamptothecin nanocrystal was long rod,and the loss of the main drug content of the high pressure homogenization method was lower than that of the wet milling method.There was no significant difference in the rate of release in 0.2% SDS-PBS（ p H = 7.4） medium（ P〉 0.05）.Conclusion The nanocrystalline suspension prepared by high pressure homogenization method eventually had uniform particle size distribution,simple process and controllable quality,and it was easy to realize process amplification.