醋氯芬酸缓释片和普通片体内外释药行为的相关性研究

Relativity Study of in Vitro and in Vivo Drug Release for Sustained Release Tablets and Conventional Tablets of Aceclofenac

目的对比研究醋氯芬酸缓释片和普通片的体外释放行为和Beagle犬体内的药动学,分析体内、体外释药行为的相关性。方法以紫外分光光度法测定两药的体外释放度,利用反相高效液相色谱法测定不同时间Beagle犬血浆中药物浓度,用DAS2.0统计软件计算有关药动学参数,Loo-Riegelman法计算体内吸收百分数,并对体内外相关性进行评价。结果醋氯芬酸缓释片体外恒速释放14h累积释放百分率在95%以上,普通片和缓释片的主要药动学参数达峰时间(tmax)为(2.833±1.169)h和(12.800±0.980)h,血浆半衰期(t1/2)为(2.650±0.261)h和(6.859±6.029)h,峰浓度(Cmax)为(23.457±8.881)μg/mL和(5.674±1.903)μg/mL,药时曲线下面积(AUC0-∞)为(113.171±16.529)μg.h/mL和(128.295±118.601)μg.h/mL,且体内外相关性较好。结论醋氯芬酸缓释片血药浓度平稳,与普通片相比可较长时间保持有效血药浓度。

Objective To compare in vitro release and in vivo pharmacokinetics in Beagle dogs between sustained release tablets and conventional tablets for aceclofenac,and to analyze in vitro-in vivo correlation.Methods In vitro drug release was detected with ultraviolet spectrophotometry and drug concentrations in Beagle dog plasma at different time were tested by RP-HPLC.DAS 2.0 statistical software was used to calculate the pharmacokinetic parameters.Loo-Riegelman method was applied to calculate in vivo absorbing percentage and in vitro-in vivo correlation was evaluated.Results Aceclofenac sustained release tablets constantly released drug for 14 h in vitro and the cumulative release was more than 95%.The major parameters of sustained release tablets and conventional tablets were tmax（2.833±1.169）h and（12.800±0.980）h;t1/2（2.650±0.261）h and（6.859±6.029）h;Cmax（23.457±8.881）μg/mL and（5.674±1.903）μg/mL;AUC0-∞（113.171±16.529）μg·h/mL and（128.295±118.601）μg·h/mL respectively,with a good in vitro-in vivo correlation.Conclusion The blood concentration of aceclofenac sustained release tablets is steady,and its effective blood concentration can be maintained for a long time compared with conventional tablets.