石杉碱甲渗透泵控释微丸的制备及其药动学研究  

Preparation and Pharmacokinetics of Huperzine A Micro-porous Osmotic Pump Pellets

作　　者：尹丽娜[1] 张雅雯[1] 陈晓晓[2] 周云琍 陈燕[2] 郑高利[1] YIN Li-na;ZHANG Ya-wen;CHEN Xiao-xiao;ZHOU Yun-li;CHEN Yan;ZHENG Gao-li(Zhejiang Academy of Medical Sciences, Hangzhou 310013, China;Department of Pharmacy, Zhejiang Chinese Medicine University, Hangzhou 310053, China)

机构地区：[1]浙江省医学科学院,杭州310013 [2]浙江中医药大学药学院,杭州310053

出　　处：《中国药学杂志》2019年第9期720-725,共6页Chinese Pharmaceutical Journal

基　　金：浙江省神经精神疾病药物研究重点实验室资助项目(2019E10021);浙江省医药卫生科技计划项目资助(2018KY349);浙江省自然科学基金项目资助(LQY18H300002)

摘　　要：目的制备石杉碱甲渗透泵控释微丸,并探讨其在Beagle犬内的药动学特性。方法采用挤出滚圆法制备渗透泵含药丸芯,以乙基纤维素和PEG400用量为考察因素结合星点设计效应面法优选包衣液处方,通过流化床包衣工艺制备石杉碱甲渗透泵控释微丸。按最优处方制备3批微丸并以累积释放度与时间进行零级、一级、Higuchi方程拟合考察其释药特性。以市售的石杉碱甲普通片为参比制剂,考察自制石杉碱甲渗透泵控释微丸的体内药动学特点,并比较两制剂的生物等效性。结果微丸最优处方为PEG400用量10. 5%,乙基纤维素用量61. 5%,所制备的石杉碱甲渗透泵控释微丸24 h内释药具有零级释放特征,释放动力以渗透压为主。自制石杉碱甲渗透泵控释微丸的tmax与ρmax明显低于参比制剂,其t1/2比参比制剂延长约1倍,相对生物利用度为95. 8%。结论 Hup-A渗透泵控释微丸在Beagle犬中有较好的缓释效果,体内相关性良好。OBJECTIVE To prepare huperzine A micro-porous osmotic pump pellets and to investigate the pharmacokinetic properties in Beagle dogs. METHODS The extrusion-spheronisation method was used to prepare the core of huperzine A pellets which then coated by fluid-bed coating technology.Central composite design-response surface method was used to optimize the prescription of coating layer.Then Zero-order, First-order and Higuchi equation of cumulative release with time were fitted to study its release characteristics.The commercially available huperzine A tablets were used as reference preparations to investigate the in vivo pharmacokinetics of huperzine A micro-porous osmotic pump pellets, and the bioequivalence of the two preparations were compared. RESULTS The formula of coating was optimized as followsEC of 61.5%, PEG400 of 10.5%. Zero-order kinetics existed in the release of the pellets in 24 h. Moreover, the osmotic pressure-controlled delivery was greatly responsible for drug release. In vivo study showed that tmax and ρmax of huperzine A micro-porous osmotic pump pellets were significantly lower than that of the reference preparation, and its t1/2 was significantly prolonged compared with the reference preparation, the relative bioavailability was 95.8%. CONCLUSION Huperzine A micro-porous osmotic pump pellets had a better sustained release effect in the Beagle dog and have a good correlation in vivo.

关 键 词：石杉碱甲 渗透泵控释微丸 星点设计效应面 零级释放 渗透压 累积释放度 药动学 

分 类 号：R944[医药卫生—药剂学]