基于平行人工膜渗透模型预测抗癌药甲磺酸仑伐替尼胶囊生物等效性

Prediction of Bioequivalence of Lenvatinib Mesilate Capsules Based on Parallel Artificial Membrane Permeability Analysis

关键词:  甲磺酸仑伐替尼胶囊  溶解度  渗透性  生物等效性

Key words:  lenvartinib mesylate capsules  parallel artificial membrane  solubility  permeability bioequivalence

摘要:

目的 采用平行人工膜渗透模型,预测自产甲磺酸仑伐替尼胶囊与参比制剂的体内生物等效性。方法 通过推测甲磺酸仑伐替尼的BCS分类,基于平行人工膜渗透模型,搭建甲磺酸仑伐替尼胶囊体外溶出-渗透速率测试模型,实时监测甲磺酸仑伐替尼胶囊和参比制剂在空腹条件模拟液以及餐后条件模拟液下的溶出度和渗透量,计算药物通过膜的通量、渗透总量。结果 在模拟空腹和餐后条件下,处方A的渗透速率和渗透量的几何均值比90%置信区间均在80.00%~125.00%范围内,处方B未落在此区间。结论 本研究方法可以预测甲磺酸仑伐替尼胶囊与参比制剂生物等效性,并具备一定的体内外相关性。

Abstract:

ABSTRACT: OBJECTIVE To predict the bioequivalence of Lenvatinib Mesilate Capsules by using the parallel artificial membrane permeability analysis. METHODS based on the BCS classification of ranvartinib mesylate and the parallel artificial membrane permeation model, the in vitro dissolution permeation rate test model of ranvartinib mesylate capsules was established, through real-time monitoring of the dissolution and penetration of lenvartinib mesylate capsules and reference preparations in fasting gastric juice, intestinal fluid and postprandial intestinal fluid, the flux and total penetration of drugs through the membrane were calculated. RESULTS in fasting state and fed state, the 90 % confidence interval of geometric mean ratio of two key quality parameters （permeation flux and permeation amount） of the preparation A all were in the range of 80.00 %-125.00 %, the preparation B did not fall into this interval. CONCLUSION this research method can predict the bioequivalence of renvartinib mesylate capsule and reference preparation, it and has a certain correlation in vivo and in vitro.