氯氮平漂浮缓释胶囊体内外相关性评价

Evaluating in vitro-in vivo correlation of clozapine floating sustained-release capsules

目的建立氯氮平漂浮缓释胶囊体内外相关性评价模型 ,评价体内外相关性。方法利用Wanger Nelson方法和卷积模型分别评价氯氮平漂浮缓释胶囊体内外相关性。通过反卷积方法由体外释放数据得到了氯氮平漂浮缓释胶囊的体内输入函数。利用基本卷积模型和扩展卷积模型预测了氯氮平漂浮缓释胶囊体内血药浓度峰值 (Cmax)和血药浓度 时间曲线下面积值 (AUC)。结果Wanger Nelson方法的相关系数为0 9798;反卷积方法得到的体内输入值与体外释药量相关性良好 ,相关系数为 0 996。扩展卷积模型预测的Cmax和AUC值与实验值误差 <6 % ;而基本卷积模型预测值误差 >2 8%。结论氯氮平漂浮缓释胶囊体内外相关性良好。应用扩展的卷积模型能很好的预测氯氮平体内血药浓度 。

Objective To develop and evaluate the internal predictability of in vitro in vivo correlation (IVIVC)models for clozapine floating sustained release capsules. Methods Using the Wanger Nelson method to evaluate the IVIVC and a deconvolution based model was attempted through a correlation of percent in vivo input obtained through deconvolution and percent in vitro dissolution obtained experimentally. Further, basic and extended convolution IVIVC models were attempted for clozapine. Internal predictability for the IVIVC models was assessed by comparing observed and predicted values for C max and AUC.Results The relative coefficient of the regression function obtained using the Wanger Nelson method was 0.9798 . The deconvolution based model got a relative coefficient as high as 0.996.Highly predictive extended convolution IVIVC models with prediction errors(PE%) of <8% could be developed.The basic convolution IVIVC models which were used in vitro dissolution as the in vivo input had PE% values > 28%.Conclusion The extended convolution IVIVC model with good internal predictability can be developed for clozapine floating sustained release capsules.