米拉贝隆缓释片的体内外相关性溶出方法研究  

Study of in vivo-in vitro correlation of mirabegron sustained-release tablets

作　　者：刘芳伶 范诗雨 周群 欧阳罗 程泽能 Fang-Ling LIU;Shi-Yu FAN;Qun ZHOU;Luo OUYANG;Ze-Neng CHENG(Xiangya School of Pharmaceutical Sciences,Central South University,Changsha 410013,China;Hunan Huize Bio-pharmaceutical Co.,Ltd,Changsha 410000,China;Hunan Engineering Research Center for Self-Emulsifying Technology Innovative Formulations,Changsha 410000,China)

机构地区：[1]中南大学湘雅药学院,长沙410013 [2]湖南慧泽生物医药科技有限公司,长沙410000 [3]自乳化技术创新制剂湖南省工程研究中心,长沙410000

出　　处：《药物流行病学杂志》2023年第6期671-678,共8页Chinese Journal of Pharmacoepidemiology

摘　　要：目的利用流通池模拟难溶性药物米拉贝隆缓释制剂的溶出,建立米拉贝隆体内和体外的相关性(IVIVC)模型,开发具有预测能力的体外溶出方法。方法经Loo-Riegelman法对三种不同释放速率制剂的体内血药浓度进行反卷积分获得相应的累积吸收百分数(Fabs%),建立体外溶出目标曲线。以纯水为试验介质,流速4.0 mL·min^(-1)的试验条件下进行制剂R(贝坦利^(■),50 mg)和制剂T1、T2(50 mg)的溶出试验,通过高效液相色谱法测定溶出度,梯形面积法获得制剂的累积溶出百分数(F_(diss)%)。结果建立了米拉贝隆缓释制剂体内累积吸收与体外溶出度之间的A级IVIVC(回归系数大于0.9),制剂的外部预测误差在规定范围内。结论本研究建立的米拉贝隆缓释制剂IVIVC模型经验证具有较好的预测能力,该方法拥有的良好区分力及线性模型也可以为质量控制提供参考。Objective To use a flow-through cell to simulate the dissolution of mirabegron sustained-release formulations to establish an in vitro-in vivo correlation(IVIVC),and to delevolp an in vitro dissolution method with predictive ability.Methods The corresponding cumulative absorption fractions(F_(abs)%)were obtained by deconvolution of the in vivo plasma concentrations of the three different release rate formulations by the Loo-Riegelman method,and the in vitro dissolution target curve was established.The concentration of reference R(Betmiga^(■),50 mg)and test T1,T2,(50 mg)formulations in the dissolution test was determined by HPLC under the test conditions of pure water as the test medium and the flow rate of 4.0 mL·min^(-1).The accumulated release fractions(F_(diss)%)of the formulation was obtained by the trapezoidal area method.Results A level A IVIVC(the coefficient>0.9)of mirabegron sustained-release formulation between the absorption in vivo and dissolution in vitro was established.The external prediction error of the formulation was within the specified range.Conclusions The IVIVC model established in this study has been verified to have good predictive ability,and the good discrimination and linearity of this method can also provide a reference for quality control.

关 键 词：米拉贝隆缓释片 体内外相关性 溶出度 流通池 

分 类 号：R927[医药卫生—药学]