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
孙晨 1李小荣 2张云鹏 2施斌 2贺敦伟1
作者信息
- 1. 中国海洋大学 医药学院,山东青岛 266003;上海则正医药科技股份有限公司,上海 201807
- 2. 上海则正医药科技股份有限公司,上海 201807
- 折叠
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Cmax、AUC0-t、AUC0-∞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.
Abstract
Objective:To explore dissolution profile characterization methods for prescription screening in scale-up 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 Cmax,AUC0-t,AUC0-∞,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 flow-through 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Key words
esomeprazole/bioequivalence/flow-through cell method/dissolution curves引用本文复制引用
出版年
2024
NETL
NSTL
万方数据