国产盐酸二甲双胍片与国际公认参比制剂溶出度比较

Dissolution Comparison Between Domestic Metformin Hydrochloride Tablets and the Internationally Recognized Reference Products

关键词:  盐酸二甲双胍  体外溶出  相似因子  国际公认参比制剂

Key words:  metformin hydrochlorid  in vitro dissolution  similarity factor  internationally recognized reference products

摘要:

目的 建立盐酸二甲双胍片溶出度测定方法，并分别比较250 mg及500 mg 2种规格国产盐酸二甲双胍片与国际公认参比制剂的溶出曲线。方法 分别以水、0.1 mol·L^-1盐酸、pH 4.0及pH 6.8磷酸盐缓冲溶液为溶出介质，采用桨法进行体外溶出度试验。用高效液相-紫外分光光度法（HPLC-UV）测定溶出介质中药物含量，并采用溶出度相似因子（f₂值）分别评价国产片（每片250 mg）与日本橙皮书Glycoran（每片250 mg）、国产片（每片500 mg）与欧盟上市Merck Santé S.A.S（每片500 mg）在各pH介质中的相似性。结果 每片250 mg的2种制剂在各溶出介质中，15 min内的溶出百分率均>85%。在0.1 mol·L^-1盐酸的溶出介质中，国产盐酸二甲双胍片（每片500 mg）与欧盟上市Merck Santé S.A.S（每片500 mg）的溶出曲线f₂值为78.5（>50）；在水、pH 4.0及pH 6.8磷酸盐缓冲溶液的溶出介质中，2种制剂的溶出曲线f₂值均<50。结论 2种规格为每片250 mg的盐酸二甲双胍片溶出行为相似。除0.1 mol·L^-1的盐酸介质外，2种规格为每片500 mg的盐酸二甲双胍片在各种溶出介质中的溶出行为不相似。

Abstract:

OBJECTIVE To establish the method of dissolution determination and compare the dissolution profiles of the two specifications of domestic metformin hydrochlorid(250 mg and 500 mg) with those of the internationally recognized reference products, respectively. METHODS The in vitro dissolution profiles of metformin hydrochlorid tablets were tested by paddle dissolving method with the dissolution media of water, 0.1 mol·L^-1 hydrochloric acid, phosphate buffer saline(PBS) of pH 4.0 and pH 6.8. Metformin hydrochlorid in the dissolution media was determined by HPLC-UV. The dissolution similarity factors(f₂) was used to evaluate the similarity of dissolution profiles between domestic tablets(250 mg per tablet) and Glycoran(250 mg per tablet) in JP-orangebook, domestic tablets(500 mg per tablet) and Merck Santé S.A.S(500 mg per tablet) received marketing approval in Europe, respectively. RESULTS The accumulative dissolution percentages of domestic and reference products(250 mg per tablet) were both >85% at 15 min. In the dissolution medium of 0.1 mol·L^-1 hydrochloric acid, the dissolution similarity factor f₂ of domestic metformin hydrochlorid tablets(500 mg per tablet) compared with Merck Santé S.A.S was 78.5(>50). In the other dissolution media(water, PBS of pH 4.0 and pH 6.8), the f₂ of test and reference products (500 mg per tablet) was <50. CONCLUSION The dissolution profile of domestic products(250 mg per tablet) is similar with reference produces. There is a significant different dissolution profile between domestic(500 mg per tablet) and reference products in various dissolution media, except in 0.1 mol·L^-1 hydrochloric acid.