黄体酮混悬注射剂药动学及体内外相关性研究
Pharmacokinetics and in vitro-in vivo correlation of progesterone suspension injection
刘兰岚 1蔡其霖 1张汶彦 1严真 2尹莉芳3
作者信息
- 1. 中国药科大学药学院药剂系,南京 210009
- 2. 江苏省缓释智能制剂及关键功能性辅料开发与评价工程研究中心,南京 210009
- 3. 中国药科大学药学院药剂系,南京 210009;江苏省缓释智能制剂及关键功能性辅料开发与评价工程研究中心,南京 210009
- 折叠
摘要
探讨黄体酮混悬注射剂体外释放、体内药动学以及体内外相关性,以自制黄体酮混悬注射液为例,采用桨法和透析袋法测定 3种不同粒径(3、5、7 μm)的黄体酮混悬注射剂的体外释放曲线;以SD大鼠为实验动物,研究 3种粒径黄体酮混悬注射剂的体内药动学,并将血药浓度-时间曲线经Wagner-Nelson法处理后得到体内累积吸收曲线,与透析袋法所得体外累积释放曲线建立体内外相关性.结果表明,黄体酮混悬注射液采用桨法测定体外释放度时,20 min内均迅速释放 85%以上,而采用透析袋法测定时分别在 40、84、120 h达 85%累积释放度.透析袋法所得体外释放趋势与体内释药趋势基本一致,相关系数大于0.95,具有较强的体内外相关性.本研究为长效混悬注射剂体内外相关性的建立提供参考.
Abstract
To investigate the in vitro release,in vivo pharmacokinetics,and the in vitro-in vivo correlation of progesterone suspension injection,self-made progesterone suspension injection was taken as an example.The in vitro release curves of three different particle sizes of progesterone suspension injections were measured using paddle method and dialysis bag method.The in vivo pharmacokinetic characteristics of self-made progesterone suspension injection was studied on SD rats.The plasma concentration of self-made progesterone preparation was detected after intramuscular injection,and correlated with the in vitro release profiles obtained by the dialysis bag method after processing by Wagner-Nelson method.The results showed that when the in vitro release of three different particle sizes of progesterone suspension injections was measured by the paddle method,more than 85%was rapidly released within 20 min,while 85%cumulative release was reached at 40 h,84 h and 120 h by dialysis bag method,respectively.The release rate obtained by the dialysis bag method was basically consistent with the in vivo release trend,with a correlation coefficient of>0.95,indicating a strong in vivo and in vitro correlation.This study provides some reference for the establishment of the in vitro and in vivo correlation of long-acting suspension injection.
关键词
黄体酮/混悬注射剂/体外释放/药动学/体内外相关性Key words
progesterone/suspension injection/in vitro dissolution/pharmacokinetics/in vitro and in vivo correlation引用本文复制引用
出版年
2024
国家科技期刊平台
NSTL
万方数据