注射用多西他赛胶束无菌检查方法验证

Sterility test validation of docetaxel micelles for injection

目的建立针对2种注射用多西他赛胶束的无菌检查方法。方法参照2015年版《中国药典》(四部)通则1105无菌检查法,取注射用多西他赛胶束15瓶,用500 mL 0.9%氯化钠溶液溶解,作为供试液,平均分配至3个滤筒过滤。同法制备6个滤筒。每个滤筒用pH 7.0无菌氯化钠-蛋白胨缓冲液冲洗3次,每次100 mL,然后加入相应培养基,并分别接种<100 CFU/mL的金黄色葡萄球菌、大肠埃希菌、枯草芽孢杆菌、白色念珠菌、生孢梭菌和黑曲霉,于适宜温度下观察培养。以等量无菌氯化钠溶液替代注射用多西他赛胶束供试液后采用相同的后续操作,作为对照组。采用薄膜过滤法,用pH 7.0无菌氯化钠-蛋白胨缓冲液冲洗滤膜,每个滤筒冲洗3次,每次100 mL,检测各菌株生长情况。结果6种验证菌株均在48 h内生长良好,样品的抑菌活性被完全消除。结论注射用多西他赛胶束可用上述方法进行无菌检查。

Objective To establish a sterility test method of docetaxel micelles for injection.Methods The method was established according to the general principles 1105 of Chinese Pharmacopoeia(2015 edition).15 bottles of docetaxel mi-celles for injection were dissolved in 500 mL 0.9%sodium chloride solution.The prepared solution was filtrated to three fil-ter cartridges at equal volume.Other three filter cartridges were prepared by the same method.Each filter cartridge was rinsed with pH 7.0 sterile sodium chloride-peptone buffer solution for three times(100 mL each time).Staphylococcus aure-us,escherichia coli,bacillus subtilis,candida albicans,clostridium sporogenes and aspergillusniger with a content less than 100 CFU/mL was respectively added in the last rinse.Then the corresponding culture medium was added and the cartridges were cultured at a suitable temperature.The same follow-up procedure was performed for the control group,in which the same amount of sterile sodium chloride solution was substituted for the test solution of docetaxel for injection.The growth of each strain was detected.Results All the six strains grew well within 48 h under suitable temperature.The antibacterial ac-tivities of the samples were completely eliminated.Conclusion The sterility test of docetaxel micelles for injection could be assayed by the established method.