艾司奥美拉唑镁肠溶干混悬剂体内外评价  

In vivo and in vitro Evaluation of Esomeprazole Magnesium Delayed-Release Oral Suspension

作　　者：孙晨 李小荣 张云鹏 施斌 贺敦伟 SUN Chen;LI Xiaorong;ZHANG Yunpeng;SHI Bin;HE Dunwei(School of Medicine,Ocean University of China,Qingdao 266003,China;HQ Pharma(Shanghai),Ltd.,Shanghai 201807,China)

机构地区：[1]中国海洋大学医药学院,山东青岛266003 [2]上海则正医药科技股份有限公司,上海201807

出　　处：《生物化工》2024年第1期24-29,共6页Biological Chemical Engineering

摘　　要：目的:探究放大生产中处方筛选的溶出曲线表征方法,筛选合适批次的制剂进行体内生物等效性研究,降低体内生物等效性试验的风险。方法:通过溶出仪桨法和流通池法对不同批次(肠溶层增重不同)的制剂进行溶出曲线表征,挑选出合适的制剂进行空腹、餐后的生物等效性研究。结果:肠溶层增重30%的制剂A和肠溶层增重32%的制剂B在0.1 mol/L盐酸-pH6.8磷酸盐缓冲液中溶出差异较小,在pH 4.5-pH 6.8磷酸盐缓冲液中,制剂A与参比制剂的溶出曲线更加拟合,受试者空腹、餐后口服制剂A后,艾司奥美拉唑的C_(max)、AUC_(0-t)、AUC_(0-∞)的几何均值比和90%置信区间均在80.00%~125.00%的等效区间内。结论:肠溶层增重30%的制剂A与参比制剂生物等效,溶出仪浆法联合流通池法可提高药物研发的效率。Objective:To explore dissolution profile characterization methods for prescription screening in scaleup production,to screen appropriate batches of formulations for in vivo bioequivalence studies,and to reduce the risk of in vivo bioequivalence testing.Methods:The dissolution curves of different batches of formulations(with different weight gain in the enteric layer)are characterized by dissolution instrument paddle method and flow-through cell method,and suitable formulations are selected for fasting state and fed state bioequivalence(BE)studies.Results:There is a small difference in dissolution between formulation A with 30%weight gain of the enteric coating layer and formulation B with 32%weight gain of the enteric coating layer in the 1.0 mol/L HCl-pH 6.8 phosphate buffer solution.In the pH 4.5-pH 6.8 phosphate buffer solution,the dissolution curves of formulation A and the reference listed drug are better fitted.As a result for fasted and fed state BE study,the geometric mean ratios of C_(max),AUC_(0-t),AUC_(0-∞),and 90%confidence interval of esomeprazole are falling within the equivalent range of 80.00%to 125.00%.Conclusion:The formulation A with a 30%weight gain in the enteric-coated layer is bioequivalent to the reference formulation,and the dissolution instrument paddle method combined with the flowthrough cell method can improve the efficiency of drug research and development.

关 键 词：艾司奥美拉唑 生物等效性 流通池法 溶出曲线 

分 类 号：R944.2[医药卫生—药剂学]