基于药物仿生系统分析雷公藤双层片的释药特征

目的: 应用药物溶出/吸收仿生系统(DDASS)研究雷公藤双层片的体外释放和跨膜透过特征,并考察其与该制剂在Beagle犬体内过程特征的体内外相关性。 方法: 以雷公藤定碱为指标成分,考察雷公藤片及雷公藤双层片在转篮法中的释药特征,研究其在DDASS模型体外连续、动态、实时的释放和跨膜透过特征;考察2种制剂在Beagle犬体内的药代动力学特征及其相应的体内外相关性。 结果: 雷公藤双层片中雷公藤定碱在转篮法和DDASS中释药过程均符合一级动力学方程,呈溶蚀释放机制。与雷公藤片相比,雷公藤双层片中雷公藤定碱在Beagle犬体内具有明显的缓释作用,相对生物利用度174.88%。在DDASS模型释放/跨膜透过特征与Beagle犬体内吸收特征存在极显著的相关性,优于转篮法溶出特征与Beagle犬体内吸收特征之间的相关性。 结论: DDASS模型可有效评价雷公藤双层片中雷公藤定碱的体外释放及体内吸收动力学特征。

Analysis on Release Characteristics of Sustained Release Traditional Chinese Medicine Preparation of Leigongteng Bilayer Tablets Based on Drug Simulating System

Objective: Taking drug dissolution and absorption simulating system (DDASS) to evaluate in vitro release and trans-membrane characteristics of Leigongteng bilayer tablets,and study in vivo and in vitro correlation between DDASS and the preparation in Beagle dogs. Method: With wilfordine as the index component,release characteristics of Leigongteng tablets and Leigongteng bilayer tablets were evaluated by the rotating basket method,in order to study in vitro continuous,dynamic,real-time release and trans-membrane characteristics in DDASS model as well as pharmacokinetic characteristics of these two preparations in Beagle dogs and their corresponding in vivo and in vitro correlation. Result: Release processes of wilfordine in Leigongteng bilayer tablets in the rotating basket method and DDASS conformed to the first-order kinetic equation and the skeleton corrosion mechanism.Compared with Leigongteng tablets,Leigongteng bilayer tablets showed obvious sustained release of wilfordine in Beagle dogs with the relative bioavailability of 174.88%.In DDASS,release/trans-membrane characteristics was significantly correlated to dog absorption characteristics,which was superior to the correlation between dissolution of the rotating basket method and Beagle dog absorption characteristics. Conclusion: DDASS model can effectively evaluate in vitro release kinetics and in vivo absorption kinetics of wilfordine in Leigongteng bilayer tablets.