基于体内外相关性的穿心莲片内酯成分溶出度测定条件的筛选  

Selection of Dissolution Conditions of Four Active Lactones in Chuanxinlian Tablets Based on in vitro and in vivo Correlation

作　　者：李鲲 王启铮 陈钧[2] 左中 张荣[1] 王奇[1] 王建新[2,3] LI Kun;WANG Qizheng;CHEN Jun;ZUO Zhong;ZHANG Rong;WANG Qi;WANG Jianxin(Science and Technology Innovation Center,Guangzhou University of Chinese Medicine,Guangzhou 510405;Key Lab.of Smart Drug Delivery(Ministry of Education),Dept.of Pharmaceutics,School of Pharmacy,Fudan University,Shanghai 201203;Institute of Integrated Chinese and Western Medicine,Fudan University,Shanghai 201203;School of Pharmacy,the Chinese University of Hong Kong,Hongkong 999077)

机构地区：[1]广州中医药大学科技创新中心,广东广州510405 [2]复旦大学药学院药剂学系,智能化递药教育部重点实验室,上海201203 [3]复旦大学中西医结合研究院药物研究所,上海201203 [4]香港中文大学药学院,中国香港999077

出　　处：《中国医药工业杂志》2020年第12期1541-1544,1545-1548,共8页Chinese Journal of Pharmaceuticals

摘　　要：为提高穿心莲片的质量控制水平,建立与体内吸收具有良好相关性的体外溶出度测定方法,本试验以穿心莲片中的活性内酯类成分为研究对象,首先采用HPLC法测定了穿心莲片中穿心莲内酯、新穿心莲内酯、14-去氧穿心莲内酯、脱水穿心莲内酯在不同pH值溶出介质(pH 1.0盐酸、pH 4.5乙酸盐缓冲液、pH 6.8磷酸盐缓冲液和水)及不同转速(50、75和100 r/min)条件下的溶出曲线;然后采用LC-MS/MS法测定Beagle犬口服穿心莲片后4种活性内酯类成分在不同时间点的血药浓度。利用Phoenix软件分别拟合穿心莲片中4种内酯的体外溶出和体内吸收过程,考察不同条件所得的体外溶出率与体内吸收分数的相关性,以确定与体内吸收具有最好相关性的体外溶出度测定条件。结果显示,4种穿心莲内酯在以pH 4.5乙酸盐缓冲液为溶出介质、转速100 r/min条件下测得的溶出率与体内吸收分数的相关性最佳,表明该条件为评价穿心莲片体外溶出的合理条件,可用来评价穿心莲片的质量。In order to establish an in vitro dissolution method with good correlation with in vivo absorption of active lactones in Chuanxinlian tablets,the dissolution profiles and pharmacokinetics in Beagle dogs of andrographolide,neoandrographolide,14-deoxyandrographolide,and 14-deoxy-11,12-didehydroandrographolide were measured.A high-performance liquid chromatography was employed to determine the dissolution rates of above four lactones from Chuanxinlian tablets in different dissolution media(pH 1.0 HCl,pH 4.5 acetate buffer,pH 6.8 phosphate buffer and water)at different rotation speeds(50,75 and 100 r/min).The plasma concentrations of four lactones in Beagle dogs after oral administration of Chuanxinlian tablets at different time intervals were analyzed with LC-MS/MS and the plasma concentration-time curves were plotted.Phoenix software was used to fit the models of in vitro dissolution and in vivo absorption fractions of four lactones in Chuanxinlian tablets.The correlation between dissolution rates and absorption fractions was established.The results indicated that there was a good correlation between the absorption rates and dissolution profiles when using pH 4.5 acetate buffer as medium and rotating at 100 r/min.It can be concluded that the dissolution in pH 4.5 acetate buffer at 100 r/min is suitable for the quality control of Chuanxinlian tablets.

关 键 词：穿心莲片 穿心莲内酯 新穿心莲内酯 14-去氧穿心莲内酯 脱水穿心莲内酯 体外溶出 体内吸收 体内外相关性 

分 类 号：R944.4[医药卫生—药剂学]