腺苷钴胺胶囊仿制药与原研药的溶出度一致性评价

Consistency Evaluation of the Dissolution of Generic and Original Preparations of Cobamamide Capsules

关键词:  腺苷钴胺胶囊  原研药  仿制药  溶出曲线  一致性评价

Key words:  cobamamide capsule  original preparation  generic preparation  dissolution curve  consistency evaluation

摘要:

目的 建立腺苷钴胺胶囊溶出度检查方法，评价其与原研药体外溶出的一致性。方法 采用HPLC测定腺苷钴胺胶囊溶出度，并进行方法学验证。分别以水、pH 1.2的盐酸溶液、pH 4.5的醋酸盐缓冲液、pH 6.8的磷酸盐缓冲液为溶出介质，溶出介质体积为500 mL，转篮法，转速50 r·min^-1，分别测定腺苷钴胺胶囊仿制药与原研药的溶出曲线，比较其体外溶出的一致性。结果 腺苷钴胺质量浓度和峰面积在一定范围内呈良好的线性关系(r≥0.999)，进样精密度、溶液稳定性、重复性试验结果均符合要求(RSD均<2%)；4种介质中的平均回收率分别为98.6%，99.6%，99.3%，101.2%，RSD分别为1.2%，0.9%，1.5%，1.8%(n=9)。在4种溶出介质中，3批腺苷钴胺胶囊与2批原研药在15 min内，累积溶出度均能>85%，均与原研药溶出曲线一致。结论 该方法可用于腺苷钴胺胶囊溶出度的检查，3批腺苷钴胺胶囊仿制药与2批原研药的体外溶出均相似，可作为体外一致性评价的方法。

Abstract:

OBJECTIVE To establish the dissolution test method of cobamamide capsules and evaluate its consistency with the original preparation in vitro. METHODS The dissolution of cobamamide capsules was determined by HPLC. The methodology was verified. Water, hydrochloric acid solution(pH 1.2), acetate buffer(pH 4.5) and phosphate buffer(pH 6.8) were used as dissolution medium, the volume of dissolution medium was 500 mL, basket method, rotating speed was 50 r·min⁻¹. The dissolution curves of cobamamide capsules generic and the original drug were measured, respectively. And the in vitro dissolution consistency was compared. RESULTS The linear relationship between mass concentration and peak area of cobamamide was good within a range(r≥0.999). The injection precision, solution stability and repeatability test results meet the requirements(RSD was all <2%). The average recoveries of cobamamide capsules were 98.6%, 99.6%, 99.3% and 101.2% in four kinds of medium, with RSD of 1.2%, 0.9%, 1.5% and 1.8%(n=9), respectively. In four kinds of medium, within 15 min the cumulative dissolution rate was >85%, which was consistent with the dissolution curve of the original preparation. CONCLUSION This method can be used to test the dissolution of cobamamide capsules. The dissolution in vitro of three batches of cobamamide capsules are similar to that of the original preparation, which can be used as a method to evaluate the consistency in vitro.