高效液相色谱法测定富马酸比索洛尔片溶出度及与原研药的一致性评价

Determination of dissolution of bisoprolol fumarate tablets by HPLC and evaluation of consistency between generic and branded drugs

目的:建立富马酸比索洛尔片的溶出度测定方法,评价国内两家厂家仿制药与原研药体外溶出行为的一致性。方法:在水、pH 1.2盐酸溶液、pH 4.0醋酸盐缓冲溶液和pH 6.8磷酸盐缓冲溶液共4种不同溶出介质中,采用桨法(转速为75 r·min^(-1))和高效液相色谱(HPLC)法(固定相为C_(18),检测波长为225 nm),分别测定仿制药和原研药的溶出度,采用相似因子(f_2)法评价溶出曲线的相似性。结果:所建HPLC法专属性良好,质量浓度在0.5～16 mg·L^(-1)范围内与峰面积具有良好的线性关系,中间精密度RSD(n=9)小于2%,回收率为90%～108%(n=3)。桨转速及溶出介质温度的微小变动均对该药的溶出行为无显著影响(P>0.05)。仿制药A与原研药4条溶出曲线的f_2分别为43,51,48和41;仿制药B与原研药4条溶出曲线的f_2分别为42,44,44和39。结论:所建HPLC法适用于富马酸比索洛尔片溶出度的测定;溶出方法耐用;富马酸比索洛尔片国产仿制药A、B与原研药的体外溶出行为均不一致。

OBJECTIVE To establish a method for the determination of dissolution of bisoprolol fumarate tablets and evaluate the consistency of in vitro dissolution behavior of generic drugs and original drugs from major domestic manufacturers.METHODS The dissolution rates of generic drugs and orignal drugs were determined in water,pH 1.2 hydrochloric acid solution,pH 4.0 acetate buffer solution and pH 6.8 phosphate buffer solution,by stirring paddle method(rotating rate 75 r·min-1)and the established HPLC method(stationary phase C18,detection wavelength 225 nm)respectively,and the similarity of dissolution profiles was evaluated by the similarity factor(f2)method.RESULTS The established HPLC method had good specificity and the concentration had a good linearity relationship with the peak area in the range of 0.5-16 mg·L-1;The RSD(n=9)of intermediate precision was lower than 2%,and recovery rates were in the range of 90%-108%(n=3).Neither slight changes of rotating rate nor temperature contributed to significant effect on the dissolution behavior of the drug(P>0.05).f2 of the dissolution profiles of generic drugs A and orignal drugs in the 4 kinds of dissolution medium were 43,51,48 and 41 respectively.f2 of the dissolution profiles of generic drugs B and orignal drugs were 42,44,44 and 39 respectively.CONCLUSION The established HPLC method is suitable for for the determination of the dissolution of bisoprolol fumarate tablets;the dissolution method is robust;the dissolution behavior of domestic generic drugs A and B of bisoprolol fumarate tablets is inconsistent with that of the branded drugs.