自制与原研托拉塞米缓释片体外释放行为的一致性评价

Study on in vitro release consistency between self-prepared Torasemide Sustained-Release Tablet and original preparation

目的建立托拉塞米缓释片的体外释放度检测方法并进行方法学研究,以所建立方法对自制与原研托拉塞米缓释片体外释放行为的一致性进行评价。方法采用HPLC法分别测定托拉塞米自制片与原研制剂在水、0.1 mol/L盐酸溶液、pH4.5醋酸盐缓冲液、pH 6.8磷酸盐缓冲液以及0.1 mol/L盐酸溶液转pH6.8磷酸盐缓冲液中的累积释放度,并用相似因子(f2)法对释放曲线的相似性进行评价。结果当托拉塞米质量浓度在1.0~12.0μg/m L时,其质量浓度与峰面积呈现良好的线性关系(r=0.999 5);精密度试验、溶液稳定性试验良好,供试液色谱峰峰面积的相对标准偏差均小于2.0%;准确度试验平均回收率为100.04%,相对标准偏差为0.54%(n=12);自制片的批内均一性符合技术要求,6个溶出杯内各取样点的相对标准偏差均<10%;托拉塞米缓释自制片与原研制剂在5种不同的释放介质中f2因子分别为72、60、77、66、60。结论本文所建立方法可用于托拉塞米缓释片释放度的检测,托拉塞米缓释片自制产品与原研产品体外释放行为一致。

Objective To establish a method for determining the dissolution of torasemide sustained-release tablet in vitro and study the methodology of the determination. The consistency of the in vitro release behavior between self-prepared torasemide sustained-release tablet and original preparation were evaluated by constructed method. Methods HPLC method was applied to detect the cumulative release percentage of self-prepared torasemide sustained-release tablet and original preparation in five kinds of release media（water, 0.1 mol/L hydrochloric acid solution, pH 4.5 acetate buffer, pH 6.8 phosphate buffer, and 0.1 mol/L hydrochloric acid solution turn to pH 6.8 phosphate buffer）. Similarity factor（f2） was used to evaluate the similarity of release curves. Results There was a good linear relationship between the quality concentration of torasemide and peak area in the range of 1.0—12.0 μg/m L（r = 0.999 5）. Results of precision and stability tests were good, and the RSDs for probational liquid were all lower than 2.0%. The average recovery of accuracy test was 100.04%, and RSD was 0.54%（n = 12）. The homogeneity of within group of self-prepared preparation met the technical requirement, RSDs of each sampling points in six Dissolution Vessels were lower than 10.0%. The f2 factors of self-prepared torasemide sustained-release tablet and original preparation were 72, 60, 77, 66, and 60 in five kinds of release media. Conclusion The method in the paper is suitable for the release test of torasemide, meanwhile, the self-prepared tablet shows consistent in vitro release behavior with that of the original preparation.