自研琥珀酸去甲文拉法辛缓释片与参比制剂体外溶出度一致性评价  

Evaluation on the in vitro release consistency between self-prepared desvenlafaxine succinate extended-release tablets and original preparation

作　　者：吴一凡 雷丽 寇同欣 邱彤 宗宏 何云柯 季晓杰 WU Yi-fan;LEI Li;KOU Tong-xin;QIU Tong;ZONG Hong;HE Yun-ke;JI Xiao-jie(China Resources Double-Crane Pharmaceuticals Co., Ltd., Beijing 100102, China)

机构地区：[1]华润双鹤药业股份有限公司,北京100102

出　　处：《药物分析杂志》2018年第6期1081-1090,共10页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:评价2种规格的自研琥珀酸去甲文拉法辛缓释片与参比制剂Pristiq^R体外溶出行为的一致性。方法:采用高效液相色谱法,色谱柱为Kromasil 100-5C_8(250 mm×4.6 mm,5μm),流动相为0.1 mol·L^(-1)磷酸二氢铵溶液(pH 4.4)-乙腈(80∶20),检测波长为226 nm,柱温为30℃,根据仿制药一致性评价要求,并参考PristiqR在FDA溶出数据库中的条件(0.9%氯化钠溶液,篮法和转速100 r·min^(-1))分别考察自研制剂与参比制剂在5种不同介质(水、0.9%氯化钠溶液、pH 1.0盐酸溶液、pH 4.5磷酸盐缓冲液及pH 6.8磷酸盐缓冲液)中的体外释放行为及其相似性,并采用乙醇倾泻和转速强力变化进一步考察两者缓释片的相似性。结果:自研制剂与参比制剂在5种不同介质中溶出曲线均相似;在强力变化的不同转速下溶出曲线相似;在乙醇倾泻实验中溶出曲线相似(f_2因子均>50%)。结论:2种规格的自研制剂与参比参比制剂体外溶出行为具有一致性。Objective：To evaluate the consistency of the in vitro release behavior between self-prepared desvenlafaxine succinate extended-release tablets and original preparation.Methods：The dissolution was analyzed by the HPLC method.Kromasil 100-5 C8（250 mm×4.6 mm,5 μm）column was used with the mobile phase of a mixture of acetonitrile and 0.1 mol·L^-1 potassium dihydrogen phosphate solution（pH4.4）.The flow rate was 1.0 m L·min^-1;the detection wavelength was 226 nm and the column temperature was 30 ℃.According to the requirement of drug consistency evaluation and the dissolution test conditions of the reference preparation（Pristiq）from FDA,the release behaviors of self-prepared desvenlafaxine succinate extended-release tablets and reference preparation in water,0.9% sodium chloride solution,pH 1.0 solution,pH 4.5 phosphate buffer and pH 6.8 phosphate buffer was investigated,respectively;the behavior under different speeds of revolution and the behavior under alcohol-induced dose dumping were analyzed.Results：The release curves of self-prepared desvenlafaxine succinate extended-release tablets were similar to those of the reference preparation under not only 5 different dissolution mediums but also different rotation speeds;furthermore,self-prepared preparation under alcohol-induced dose dumping showed the same release behavior to the original preparation（f2 factor50%）.Conclusion：The self-prepared preparation of two strength and the reference preparation showed consistency in vitro release behavior.

关 键 词：琥珀酸去甲文拉法辛 缓释片 药品一致性评价 药物体外溶出度 溶出曲线 倾泻实验 F2因子 

分 类 号：R917[医药卫生—药物分析学]