富马酸喹硫平缓释片的体内外相关性溶出方法研究

In vitro-in vivo correlation of dissolution method for quetiapine fumarate sustained-release tablets

目的通过流通池法模拟富马酸喹硫平缓释制剂的体内动力学过程,建立具有体内外相关性的溶出方法,并进行体内外相关性模型预测能力的评估。方法采用HPLC-MS/MS法测得T1、T2和R制剂的血药浓度数据,通过WinNonlin软件的非房室模型和反卷积模块解析参比制剂的体内特征,依据参比制剂的体内特征指导溶出方法的设计,用3种释放速率不同的制剂的体内和体外数据建立体内外相关性模型,并进行模型预测能力验证。结果建立了具有A级相关性(R^(2)=0.967)和C级相关性(R^(2)=0.996)的溶出方法,内部制剂预测和外部制剂预测的预测误差PE%<10%,符合标准。结论本方法具有良好的体内外相关性,其体内外相关性模型经验证预测误差符合标准,对于吸收速率不同的制剂均具有良好的区分力,可以为富马酸喹硫平缓释片的制剂评价提供参考。

Objective To simulate the in vivo kinetics of quetiapine fumarate sustained-release preparations by flow cell method,to establish a dissolution method with in vitro and in vivo correlation,and to evaluate the predictive ability of the in vivo and in vitro correlation model.Methods The blood concentration data of T1,T2 and R preparations were measured by HPLC-MS/MS method.Then,the in vivo characteristics of the reference preparation were analyzed by the non-compartmental model and deconvolution module of WinNonlin software.Finally,the dissolution was guided according to the in vivo characteristics of the reference preparation.The in vitro and in vivo correlation models were established with in vivo and in vitro data from the 3 formulations with different release rates,and the model predictive proficiency was validated.Results A dissolution method with A-level correlation(R^(2)=0.967)and C-level correlation(R^(2)=0.996)was established.The prediction error PE%was<10%for both the internal formulation prediction and external formulation prediction,in line with the standard.Conclusion The dissolution method established in this study has good in vitro and in vivo correlation.The correlation model has been verified to meet the standard prediction error,has good discrimination power for various preparations with different rates,and can provide reference for the formulation evaluation of quetiapine maleate sustained-release tablets.