基于单池药物溶出/吸收仿生系统评价格列吡嗪不同制剂的释药特征及其体内外相关性

Studies on release characteristics of different preparation of glipizide and intrinsic and exoteric correlation based on Single cell drug dissolution/absorption simulating system

关键词:  单池药物溶出/吸收仿生系统  格列吡嗪  体内外相关性

Key words:  Single cell drug dissolution/absorption simulating system  glipizide  in vitro/in vivo correlation

摘要:

[目的] 考察格列吡嗪片及其缓释片在单池药物溶出/吸收仿生系统（Single cell-DDASS）的释放特征，以及与比格犬体内吸收程度的相关性。[方法] 采用《中华人民共和国药典》（以下简称《药典》）溶出度法和Single cell-DDASS法对格列吡嗪片及其缓释片进行体外释放度实验，用Wagner-Nelson方程计算不同格列吡嗪制剂在体内的吸收百分数，并与相应时间点体外累积释放度进行线性回归，进一步考察其体内外相关性（IVIVC）.[结果] 格列吡嗪缓释片体外释放度的最优拟合方程是一级动力学方程，释放机制为溶蚀机制。格列吡嗪片在《药典》溶出法中释放过快，无法建立体内外相关性，而Single cell-DDASS法中累积释放度与比格犬体内吸收百分数之间存在相关性（r=0.773 2，P<0.05）.格列吡嗪缓释片在《药典》溶出法中累积释放度与比格犬体内吸收百分数之间密切相关（r=0.811 5，P<0.05）.格列吡嗪缓释片在Single cell-DDASS法中累积释放度与比格犬体内吸收百分数之间极密切相关（r=0.987 7，P<0.01）.[结论] 格列吡嗪片及其缓释片在Single cell-DDASS法中累积释放度与比格犬体内吸收百分数之间的相关性明显优于《药典》溶出法释放百分数与比格犬体内吸收百分数的相关性，表明Single cell-DDASS能够良好预测格列吡嗪不同制剂在体内的动力学特征。

Abstract:

[Objective] To study the drug release characteristics in Single cell drug dissolution/absorption simulating system (Single cell-DDASS) and the correlation between the dissolution in vitro and the absorption in vivo of glipizide immediate release tablet and glipizide sustained release tablet. [Methods] The release characteristics of glipizide different preparation were investigated using dissolution testing described in Pharmacopoeia of the People's Republic of China (CHP) and Single cell-DDASS. Single-dose pharmacokinetic studies for the tablets were carried out in six beagle dogs. The percent in vivo absorption in beagle dogs was calculated by Wagner-Nelson method. The correlations between release characteristics in both CHP method and Single cell-DDASS and in vivo absorption were investigated. [Results] The release pattern of glipizide sustained release tablet in vitro could be described by zero-order kinetics and release mechanism was attributed to the dissolution mechanism. Glipizide immediate release tablet dissolution was fast in CHP method and in vitro/in vivo correlation could not be established. The correlation, however, between glipizide immediate release tablet release characteristics in Single cell-DDASS and the absorption in beagle dogs was significant (r=0.773 2, P<0.05). The correlation between release characteristics of glipizide sustained release tablet in CHP method and the absorption in beagle dogs was significant (r=0.811 5, P<0.05); the correlation between release characteristics of glipizide sustained release tablet in Single cell-DDASS method and the absorption in beagle dogs was also significant (r=0.987 7, P<0.01). [Conclusion] There is a significant correlation between Single cell-DDASS release and absorption of beagle dogs for glipizide immediate release tablet and glipizide sustained release tablets, and the correlation degree is higher than that between dissolution test described in CHP method and absorption in beagle dogs. Single cell-DDASS can be used to evaluate the in vivo absorption of glipizide immediate release tablet and sustained release tablet.