多奈哌齐缓释微球的制备及家兔体内药动学研究  

Preparation of Donepezil Sustained Release Microspheres and Pharmacokinetic Research in Rabbits

作　　者：皮佳鑫[1] 王浩[2] 栾瀚森[2] 杨莉[2] 

机构地区：[1]天津中医药大学,天津300193 [2]药物制剂国家工程研究中心,上海201203

出　　处：《中国药学杂志》2013年第15期1284-1288,共5页Chinese Pharmaceutical Journal

摘　　要：目的通过超声波技术制备多奈哌齐缓释微球。方法应用超声波装置制备多奈哌齐缓释微球，进行载药量、粒径、体外释放实验等体外评价，并用LC—MS／MS研究多奈哌齐微球家兔体内的药动学。结果应用超声波装置制备多奈哌齐缓释微球，载药量为12．1％，粒径分布在40～130μm，体外可累计释药一个月，经家兔皮下单剂量30．0mg·kg^-1注射给药，主要药动学参数为：ρmax=40．63μg·L^-1，tmax=2．47d，MRT=14．81d，AUC0→∞=646．96μg·d·L^-1。结论应用超声波技术成功制备具有明显缓释特性的多奈哌齐微球。OBJECTIVE To prepare and evaluate donepezil sustained-release microspheres by ultrasound technique. METHODS Preparation technology of donepezil biodegradable microspheres by ultrasound technique was established and optimized. In vitro evaluation of donepezil microspheres was carried out. The pharmacokinetics of donepezil microspheres was investigated by LC-MS/MS after subcutaneous injection in rabbits at a dose of 30. 0 mg · kg^-1. RESULTS Donepezil microspheres with drug loading of 12. 1% and mean particle size between 40 to 130 p.nl were successfully prepared by ultrasound technique. The donepezil microspheres displayed a one-month sustained-release character in vitro. The pharmaeokinetic parameters were as follows ： ρmax 40. 63 μg · L ^- 1 , tmax 2.47 d, MRT 14. 81 d,and AUC0→∞ 646. 96 μg · L^-1. CONCLUSION Ultrasound technique is successfully applied in the preparation of donepezil sustained-release microspheres.

关 键 词：多奈哌齐 乙交酯丙交酯共聚物 缓释微球 超声波技术 

分 类 号：R944[医药卫生—药剂学]