高剪切工艺制备阿立哌唑长效注射混悬剂  

Preparation of aripiprazole long-acting injectable suspension by high-shear rotor-stator wet milling

作　　者：朱思琪 刘坤鹏 邹佳 李海燕 王丹 王震 ZHU Si-qi;LIU Kun-peng;ZOU Jia;LI Hai-yan;WANG Dan;WANG Zhen(Zhejiang Sundoc Pharmaceutical Science and Technology Co.,Ltd.,Hangzhou 310051)

机构地区：[1]浙江圣兆药物科技股份有限公司,杭州310051

出　　处：《中南药学》2024年第8期2006-2011,共6页Central South Pharmacy

摘　　要：目的优化阿立哌唑长效注射混悬剂的制备工艺。方法采用高剪切工艺制备阿立哌唑长效注射混悬剂,考察定转子类型、线速度、定转子间距、助悬剂浓度、药物浓度、料液温度对药物粒径的影响,并与球磨法制备的样品对比颗粒形貌、体外释放、体内缓释效果。结果最优制备工艺为:以胶体磨模块作为剪切头,药物浓度为13%,羧甲基纤维素钠浓度为0.52%,辅料溶液pH为5.0~6.0,转子线速度为35 m·s^(-1),定转子间距为100μm,料液温度在48~65℃,得到阿立哌唑长效注射混悬剂的平均粒径为(3.83±0.05)μm。与球磨法制备的样品相比,具有更好的分散性,药物颗粒更为圆滑,以及具有更为优异的体内外缓释效果。结论通过高剪切工艺制备阿立哌唑长效注射混悬剂,制备工艺简便,易于放大生产,并实现了较好的缓释效果,对其他药物的开发具有一定的参考价值。Objective To optimize the preparation of aripiprazole(APZ)long-acting injectable suspension(LAIs).Methods APZ LAIs were prepared by high-shear rotor-stator wet milling.Effect of types of the rotorstator,rotation tip speed,gaps of the rotor-stator,concentrations of suspension agent,drug concentrations and material temperature on the particle size were determined.APZ LAIs were characterized by surface morphology,in vitro release and the sustained release effect in vivo,and compared with samples prepared by wet media milling.Results The optimal conditions for the preparation of APZ LAIs included module colloid mill as a shear tool,the drug concentration at 13%,the carboxymethylcellulose sodium concentration at 0.52%,the pH of excipients solution at 5.0~6.0,the rotation tip speed at 35 m·s^(-1),the gap of the rotorstator at 100μm,and the material temperature at 48~65℃.The obtained average particle size of APZ LAIs was(3.83±0.05)μm.Compared with the samples prepared by wet media milling,APZ LAIs had better dispersion without aggregation,with smoother surface and shape,and more excellent sustained release effect in vitro and vivo.Conclusion The preparation of APZ LAIs is simple and convenient,feasible for mass production.This study provides a reference for the development of other drugs.

关 键 词：阿立哌唑 长效注射混悬剂 高剪切工艺 体外释放 体内释药 

分 类 号：R944.9[医药卫生—药剂学]