尼莫地平缓释软胶囊体内外相关性研究

 目的考察不同释放介质中尼莫地平缓释软胶囊的释药动力学,研究尼莫地平缓释软胶囊在家兔体内的生物利用度,建立体内外相关性方程。方法释放度实验采用转篮法分别在两种介质中进行;以高效液相色谱法测定血药浓度,以3P87药动学软件进行拟合,并计算相对生物利用度;分别以室模型法和反卷积分法对体外累积释药和体内吸收分数进行拟合,求算体内外相关性方程。结果缓释软胶囊与普通软胶囊相比,t_max明显延长,ρ_max显著降低,t_1/2及MRT延长;相对生物利用度为113.4%;以0.5%SLS醋酸钠缓冲溶液(pH4.5)为释放介质时体外释放与体内生物利用相关性良好,在该介质中药物的释放为非Fickian扩散,释放机制为扩散和骨架溶蚀的协同作用。结论尼莫地平缓释软胶囊具有明显的缓释特征,在不同释放介质中呈现不同的释药机制;以0.5%SLS醋酸钠缓冲溶液(pH4.5)为介质可获得良好的体内外相关性。

Release Kinetics and in Vitro-in Vivo Correlation of Nimodipine Sustained-release Soft Gelatin Capsule

OBJECTIVE To study the release kinetics of nimodipine(NMP) sustained-release soft gelatin capsules (SGC),to investigate its bioavailability in rabbits and to develop a correlation between in vitro release and in vivo absorption. METHODS Dissolution study was carried out in two media, using the rotary basket method. HPLC method was developed to determine plasma concentration. The plasma concentration-time curve was fitted by the 3P87 software and relative bioavailability was studied. Compartment model and deconvolution technique were used to explain the in vitro-in vivo correlation.RESULTS Compared with commercial NMP-SGC, tmax,MRT and t_1/2 of sustained-release NMP-SGC were prolonged, its ρ_max was decreased and its relative bioavailability was 113.4%. When pH 4.5 acetate buffer solution containing 0.5%SLS was used as dissolution medium, a good in vitro-in vivo correlationship was obtained. The cumulative drug release was explained by non-Fickian diffusion in which both diffusion and erosion were involved. CONCLUSION The sustained-release NMP-SGC shows sustained-release character and the release kinetics varied with release media.A good in vitro-in vivo correlation is obtained in the pH 4.5 acetate buffer solution containing 0.5%SLS.