非水溶液氯硝西泮注射剂无菌检查法的研究

Study on Sterility Test of Non-aqueous Clonazepam Injection

目的 建立非水溶液氯硝西泮注射液无菌检查方法,探索有机溶剂对于无菌检查法的影响。方法 参考《中国药典》2020年版,通过薄膜过滤法无菌检查及膜通透性实验,考察氯硝西泮注射液中有机溶剂对集菌培养器不同材质的滤膜及杯体的影响,以及样品溶液pH值,冲洗液的品种及数量对样品中微生物的影响。结果 苯甲醇、冰醋酸及无水乙醇会造成集菌培养器复合纤维素膜、尼龙膜及聚偏二氟乙烯(PVDF)膜不同程度溶解,复合纤维素膜溶解程度更严重,残留于杯体及滤膜的苯甲醇不溶于培养基造成浑浊;丙二醇与AS杯体反应故培养基呈浑浊。不同冲洗液冲洗后培养基pH范围在5.99~7.16之间。结论 建立了一种合理的无菌检验方法,该方法为其他以有机相为溶剂的注射液无菌检查提供较好的参考价值。

Objective To establish a method for sterility test of non-aqueous clonazepam injection,and explore the effect of organic solvent on sterility test.Methods With reference to the 2020 edition of Chinese Pharmacopoeia,the effects of organic solvents in Clonazepam injection on the filtration membranes and cups of different materials of the collector were investigated by membrane filtration test and membrane permeability test,as well as the effects of pH value of the sample solution and the variety and quantity of the rinsed solution on the microorganisms in the sample.Results Benzyl alcohol,acetic acid and anhydrous ethanol caused the dissolution of composite cellulose membrane,nylon membrane and PVDF membrane in different degrees,and the dissolution of composite cellulose membrane was more serious,and the benzyl alcohol remaining in the cup and filter membrane was insoluble in the medium and caused turbidity.The reaction of propylene glycol with AS cup made the medium cloudy.The pH range of the culture-medium was 5.99~7.16 after washing with different rinsing solutions.Conclusions We have developed a rational sterile testing method,which provides a good reference value for the sterile inspection of injections using organic phases as solvents.