恩格列净缓释微丸处方工艺的研究  

Research on the formulation and technology of Empagliflozin sustained-release pellets

作　　者：万旭春 王晶 张艺蓉 李翰铭 赵利刚 WAN Xuchun;WANG Jing;ZHANG Yirong;LI Hanming;ZHAO Ligang(Tangshan Key Lab.of Novel Preparations and Drug Release Technology,School of Pharmacy,North China University of Science and Technology,Tangshan,Hebei,063210 P.R.China)

机构地区：[1]华北理工大学药学院唐山市新型药物制剂与释药技术重点实验室,河北唐山063000

出　　处：《华西药学杂志》2022年第4期370-375,共6页West China Journal of Pharmaceutical Sciences

基　　金：华北理工大学杰出青年基金项目(JQ201713)。

摘　　要：目的制备恩格列净载药微丸与缓释微丸,并测定载药率与研究其体外释放度。方法采用包衣液液相层积法与流化床底喷包衣技术结合制备缓释微丸,以载药率与释放度为评价指标,通过正交设计优化流化床的载药参数,Box-Behnken实验设计优化缓释层处方。结果载药层处方为:0.75 g恩格列净原料药、1.50 g羟丙基甲基纤维素、30 g 70%乙醇;流化床参数为:进风量14 m^(3)·h^(-1)、进风温度55℃、包衣液流速1 mL·min^(-1);缓释层处方为:5.70 g乙基纤维素、0.18 g聚乙二醇、0.57 g柠檬酸三乙酯、0.30 g滑石粉,所得恩格列净缓释微丸的4 h释放度小于30%,12 h释放度为60%~70%,20 h释放度大于80%。结论所用工艺简单易行,操作性强,所得恩格列净微丸的载药率较高,恩格列净缓释微丸的缓释效果明显,释药行为良好,有一定的开发价值。OBJECTIVE To prepare Empagliflozin drug-loaded pellets and sustained-release pellets,and carry out the determination of drug loading rate and the study of in vitro release.METHODS Sustained-release pellets of Empagliflozin were prepared by combining the liquid phase coating stratification method and fluidized bed bottom spray technology.The drug loading rate and release rate were used as indicators to optimize the fluidized bed parameters through an orthogonal design.In order to increase the drug loading rate,Box-Behnken experimental design was used to optimize the formulation of sustained-release layer.RESULTS Drug-loading layer prescription was as follow:Empagliflozin bulk drug of 0.75 g,hydroxypropyl methylcellulose of 1.50 g,and 70%ethanol aqueous solution of 30.00 g.The optimized parameters for fluidized bed were inlet air volume of 14 m^(3)·h^(-1),inlet air temperature of 55℃and coating liquid flow rate of 1 mL·min^(-1).The sustained-release layer prescription was EC 5.7 g,PEG 0.18 g,TEC 0.57 g,talc 0.30 g.The release rates of pellets in 4 h,12 h and 20 h were respectively less than 30%,60%-70%,and greater than 80%.CONCLUSION This process is simple and easy to implement,and of strong operability.The prepared Empagliflozin pellet has a high drug loading rate,and the prepared Empagliflozin sustained-release pellet has obvious slow-release effects and good drug release behavior,and has certain research and developmental value.

关 键 词：恩格列净 恩格列净载药微丸 恩格列净缓释微丸 高效液相法 流化床包衣 液相层积法 正交分析法 Box-Behnken实验设计 

分 类 号：R94[医药卫生—药剂学]