环孢素软胶囊原研药与仿制药体外一致性评价

Evaluation of Dissolution Profiles in Vitro Between Brand Name Drug and Generics of Cyclosporine Capsules

关键词:  环孢素  溶出曲线  一致性  相似因子(f₂)

Key words:  cyclosporine  dissolution profiles  consistency  similarity factors(f₂)

摘要:

目的 比较国产环孢素软胶囊与进口原研药在4种不同溶出介质中溶出曲线的一致性。方法 以水、0.1 mol·L^-1盐酸、pH 4.5醋酸盐缓冲溶液和pH 6.8磷酸盐缓冲溶液为溶出介质，分别测定其溶出曲线，并采用f₂因子来考察其相似性。结果 国产环孢素软胶囊3批样品在水中的溶出曲线与原研药均存在差异(f₂均<50，f₂平均值为40.20，RSD为2.53%)，在0.1 mol·L^-1盐酸，pH 4.5醋酸盐缓冲溶液和pH 6.8磷酸盐缓冲溶液3种介质中的溶出曲线与原研药相似性较高(f₂均>50，f₂平均值分别为61.60，63.56，81.57，RSD分别为2.23%，3.15%，0.45%)。结论 国产环孢素软胶囊在水以外的其他3种介质中的溶出曲线与原研药相似性较高，但在水中的溶出曲线与原研药存在差异，提示两者在工艺上存在差异。

Abstract:

OBJECTIVE To compare the dissolution profiles of brand name drug and generics of cyclosporine capsules in four different mediums. METHODS The dissolution profiles of brand name drug and generics of cyclosporine capsules in water, 0.1 mol·L^-1 hydrochloric acid solution, pH 4.5 acetate buffer and pH 6.8 phosphate buffer were determined and the similarity was investigated according to the similarity factors(f₂). RESULTS The dissolution profile of three batches of generics were all different from brand name drug in water(f₂<50, the average f₂ was 40.20, RSD was 2.53%), there were high similarity of the dissolution profiles of generics and brand name drug in 0.1 mol·L^-1 hydrochloric acid solution, pH 4.5 acetate buffer and pH 6.8 phosphate buffer(f₂>50, the average f₂ were 61.60, 63.56, 81.57 in order, RSD were 2.23%, 3.15%, 0.45% in order). CONCLUSION The dissolution profile of generics is different from brand name drug in water. while the dissolution profiles of generics are similar to brand name drug in other three mediums. so there may be some differences in the manufacturing process between the brand drug and generics, which should be paid attention on in clinical use.