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.
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)
出处
《生物化工》
CAS
2024年第1期24-29,共6页
Biological Chemical Engineering
关键词
艾司奥美拉唑
生物等效性
流通池法
溶出曲线
esomeprazole
bioequivalence
flow-through cell method
dissolution curves
作者简介
孙晨(1999-),男,山东新泰人,硕士在读,研究方向为药物制剂;通信作者:贺敦伟(1981-),男,山东滨州人,博士在读,研究方向为药物递送系统。E-mail:hedunwei@hqdds.com。
