剂量分割法评价甘氨酸茶碱钠缓释片体内释放度及其体内外相关性

Application of the dose-division method in the in vivo release kinetics evaluation of the sodium theophylline glycinate sustained release dosage forms

目的以剂量分割法分析甘氨酸茶碱钠缓释片(STG-ST,平喘药)的体内外释放相关性,并与Wagner-Nelson法进行比较。方法根据剂量分割法原理,计算STG-ST体内释放动力学;以Wagner-Nelson法,采用不同吸收速率常数计算STG-ST的体内吸收度。结果Wagner-Nelson法计算药物吸收度时,直接使用缓控释制剂的表观动力学参数,容易导致方法学错误;而剂量分割法得到的体内释放度与体外释放度相关性良好。结论无需注射剂作为参比,剂量分割法适合于缓释/控释制剂体内外相关性评价。

Objective To evaluate the in vivo release behavior and its correlation with the in vitro release profile of sodium theophylline glycinate sustained release tablets （ STG - ST） by the dose - division method in comparison with the correlation of absorption and release kinetics by Wagner - Nelson method. Methods The in vivo release profile of STG - ST was processed based upon the principles of the dose - division method, while the absorption profiles were processed by Wagner- Nelson method using two eliminate rate constants. Results The direct application of the Wagner- Nelson method to the controlled/sustained release systems might lead to methodological mistakes by using the apparent eliminate rate constant of the controlled/sustained release systems. The in vivo release profile by dose - division method was well correlated with the in vitro release kinetics of STG - ST. Conclusion The dose - division method is a novel and effective way for the in vitro - in vivo correlation - ship evaluation with no requirement of the injection parameters.