摘要
目的 以空白丸芯为载体、醋酸羟丙甲纤维素琥珀酸酯为包衣材料制备盐酸度洛西汀肠溶微丸胶囊,并以市售参比制剂欣百达对照进行犬体内药动学研究。方法 采用底喷流化床包衣技术进行载药和包衣,制备盐酸度洛西汀肠溶微丸,分别采用扫描电镜、溶出度与释放度测定法对自制和参比制剂的结构和释放行为进行对比。采用LC-MS/MS法测定自制和参比制剂在犬体内药动学。结果 自制和参比制剂结构近似,包衣增重为20%的自制制剂与参比制剂释放曲线的f相似因子为75,释放曲线相似。两制剂的AUC和AUC的统计结果等效,表明两制剂在犬体内的药物吸收程度基本一致。c参数的个体内变异系数较大导致统计结果超出了规定范围。结论 自制制剂与参比制剂欣百达体外释放行为一致,比格犬体内具有相似的药时曲线。
Objective To prepare duloxetine hydrochloride enteric release capsules and to study pharmacokinetic profile in dogs with Cymbalta as reference.Methods The Wurster fluid bed with bottom spray was used to prepare duloxetine hydrochloride enteric release pellets.The SEM and in vitro dissolution tests were performed to evaluate the microstructure and drug release behavior of home-made dosage form and Cymbalta.The LC-MS/MS method was developed to study the pharmacokinetic profile of home-made dosage form and Cymbalta.Results The home-made dosage forms showed similar microstructure with Cymbalta.The home-made dosage forms at 20% coating weight gain showed similarity factor(f) of 75,indicating the similar in vitro release profiles.The home-made dosage form showed comparable absorption extent with Cymbalta as characterized by the bioequivalent AUCand AUC.The statistics of cwas beyond the acceptance range due to the large variation coefficient and small subjects.Conclusion The home-made dosage form demonstrated similar in vitro release behavior and pharmacokinetics curve with Cymbalta in beagle dogs.
作者
王嘉平
熊晓崴
常琦
乔明曦
WANG Jiaping;XIONG Xiaowei;CHANG Qi;QIAO Mingxi(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China;Yantai Luyin Pharmaceuical Co.Ltd.Yantai 264000,China)
出处
《沈阳药科大学学报》
CAS
CSCD
北大核心
2022年第8期899-905,共7页
Journal of Shenyang Pharmaceutical University
关键词
盐酸度洛西汀
肠溶微丸
流化床
包衣
药动学
duloxetine hydrochloride
enteric release capsule
fluid bed
coating
pharmacokinetics
