氨茶碱片仿制药与参比制剂体外溶出一致性评价研究

In Vitro Dissolution Consistency Evaluation Study of Generic Aminophylline Tablets with Reference Preparations

目的:建立氨茶碱片溶出测定方法,考察10家国产仿制制剂与参比制剂在4种溶出介质中体外溶出曲线的相似性以及10批参比制剂批间、批内的均一性。方法:采用中国药典溶出度测定法第二法,以pH 1.2缓冲液、pH 4.0缓冲液、pH 6.8缓冲液和水900mL为溶出介质,转速为每分钟50转;采用高效液相色谱法测定各个时间点的溶出量,色谱柱为依利特BDS(5μm,4.5×250 mm),流动相为甲醇-0.12%戊烷磺酸钠溶液(20∶80)(用冰醋酸调节pH值至2.9±0.1),检测波长为254 nm,进样体积为20μL。结果:测定方法的线性、精密度、回收率试验均符合要求,10批参比制剂在5 min时的溶出量均在27%~33%范围内,30min时的累积溶出量均达100%,国产仿制制剂5 min时的溶出量均大于50%,30 min时的累积溶出量均达100%。结论:所建立的方法专属性强,准确度高,可用于氨茶碱片体外溶出曲线的测定;10批参比制剂批间、批内均一性良好,10个厂家的国产仿制制剂在4种溶出介质中均有突释,与参比制剂在体外溶出存在差异。

Objective:To establish a dissolution assay method for Aminophylline tablets,and to investigate the similarity of the in vitro dissolution profiles of 10 domestic formulations and the reference formulation in 4 dissolution media as well as the inter-batch and intra-batch homogeneity of 10 batches of the reference formulation.Methods:The second method of Chinese Pharmacopoeia dissolution assay was adopted,and 900 mL of pH 1.2 buffer,pH 4.0 buffer,pH 6.8 buffer and water were used as the dissolution medium at a rotational speed of 50 revolutions per minute;and the dissolution amount at each time point was determined by high performance liquid chromatography(HPLC)on a column of Elite BDS(5μm,4.5×250 mm),with a mobile phase of methanol-0.12%pentanes The mobile phase was methanol-0.12%sodium pentanesulfonate solution(20∶80)(pH adjusted to 2.9±0.1 with glacial acetic acid),the detection wavelength was 254 nm,and the injection volume was 20μL.Results:The linearity,precision,and recovery of the assay method met the requirements,and the dissolution amount of the 10 batches of the reference preparations was in the range of 27%~33%at 5 min,and the cumulative dissolution amount at 30 min reached 100%.The dissolution amount of the 10 batches of reference preparations was in the range of 27%~33%at 5 min,and the cumulative dissolution amount reached 100%at 30 min.Conclusion:The established method is proprietary and accurate,and can be used for the determination of the in vitro dissolution profile of Aminophylline tablets.10 batches of reference preparations had good inter-batch and intra-batch homogeneity,and the domestic preparations of 10 manufacturers had sudden release in 4 dissolution media,which differed from that of the reference preparations in the in vitro dissolution profiles.