注射剂瓶容器密封完整性:微生物挑战法与色水法的关联比较分析

Integrity of Sealed Injection Bottle Container:Correlation and Comparative Analysis of Microbiological Challenge Test and Dye Ingress Method

考察了微生物挑战法和色水法对中性硼硅玻璃管制注射剂瓶容器密封完整性的关联并进行比较分析。微生物挑战法是将密封、灭菌后的空包装系统浸入高浓度铜绿假单胞菌的菌悬液中,施加特定压力驱动并保持4 h,取出后于33℃培养7 d;色水法是将密封后的空包装系统浸没于10%亚甲基蓝水溶液中,放入真空箱中抽至75 kPa并保持30 min,恢复常压后继续浸没30 min,取出,冲洗,目视检查。结果显示,微生物挑战法和色水法对1、3、5、10µm孔径的打孔样品阳性检出率分别为0、30%、40%、100%和0、0、4.5%、15%;10%阳性检出率的灵敏度分别为2.2、8.3μm。说明对于注射剂瓶包装,微生物挑战法的灵敏度略优于色水法,为容器密封完整性的方法开发和比较分析提供了参考。

The correlation between the microbiological challenge test and dye ingress method on the sealing integrity of the neutral borosilicate glass controlled injection bottle container was investigated and compared.The microbiological challenge test included immersion of the sealed and sterilized empty packaging system in a suspension of high concentration of Pseudomonas aeruginosa,and driving a specific pressure for four hours.After taking it out,it was cultured at 33℃for seven days.The dye ingress method was to immerse the sealed empty packaging system in a 10%methylene blue aqueous solution,then put it in a vacuum chamber with the pressure of 75 kPa for 30 min.After returning to normal pressure,it was immersed in the methylene blue solution again for 30 min,then after flushing,it was inspected visually.The results showed that the positive detection rates of microbiological challenge test and dye ingress method for punched samples with 1,3,5,and 10µm pore size were 0,30%,40%,100%and 0,0,4.5%,15%,respectively.The sensitivities of the 10%positive detection rate were 2.2 and 8.3μm,respectively,which indicated that the sensitivity of the former method was slightly better than that of the latter for injection bottle packaging.It was hoped to provide a reference for method development and comparative analysis of container seal integrity.