胞磷胆碱钠的葡萄糖注射液和氯化钠注射液的灭菌稳定性

目的研究3种规格胞磷胆碱钠葡萄糖注射液(CG)和4种规格胞磷胆碱钠氯化钠注射液(CS)的灭菌稳定性,为选择适宜灭菌工艺提拱参考。方法分别测定5种不同灭菌条件下,灭菌前后注射液的pH值、有关物质及340和700 nm波长处吸光度差值,并考察对小鼠的毒性。结果灭菌后CG的pH值明显降低,吸光度差值增高,规格为0.5 mg/mL的CG在5种灭菌条件下、规格为2.5和2 mg/mL的CG在F0>12灭菌条件下灭菌后,有关物质超过中国药典规定的限度。灭菌后CS的pH值有一定程度降低,吸光度差值不变,有关物质稍有增加,均未超过中国药典限度。两种输液灭菌后均未引起小鼠急性毒性反应。结论 0.5 mg/mL CG不适合采用终端灭菌法,2.5和2 mg/mL CG不宜选择过度杀灭法(F0>12),可考虑采用残存概率法(8≤F0<12)进行灭菌,但应保证产品灭菌后的SAL≤10-6。与CG相比,CS更适合制为大容量注射剂。

The sterilization stability for Citicoline Sodium and Glucose Injection and Citicoline Sodium and Sodium Chloride Injection

Purpose To study the sterilization stability of Citicoline Sodium and Glucose Injection(CG)and Citicoline Sodium and Sodium Chloride Injection(CS),so as to provide reference to the manufacturers for selecting the appropriate sterilization process.Methods The pH value,related substances content and absorption of CG and CS before and after sterilization(five different sterilization conditions)were determined.The mice toxicity test was conducted.Results After sterilization,the pH value of CG decreased significantly and the absorption increased.A significant increase occurred in related substances content.The related substances content of CG(0.5 mg/mL)has already exceeded the ChP(2010)limits after five different sterilizations.The related substances content of CG(2.5,2 mg/mL)has already exceeded the ChP(2010)limits after overkilled sterilization(F0>12).After sterilization,the pH value of CS decreased,the absorption did not change,the related substances content increase slightly and did not exceed the ChP(2010)limits.The mice toxicity was not caused by both.Conclusion CG(0.5 mg/mL)should not choose terminal sterilization process,and CG(2.5,2 mg/mL)should choose residual probability method(8≤ F0<12)as the sterilization process instead of overkilled sterilization(F0>12),but should ensure SAL≤10-6.Compared to CG,CS is more suitable for large volume injection.