目的: 建立人血白蛋白注射液注射剂瓶包装系统密封完整性的研究方法。方法: 针对人血白蛋白注射液注射剂瓶包装系统,采用玻璃微量移液管制备了1 μm阳性对照样品,采用激光打孔制备了2、5和10 μm的阳性对照样品。使用真空衰减法和高压放电法2种确定性的密封完整性测试方法进行方法参数开发和测试。结果: 真空衰减法因人血白蛋白药物制剂堵塞漏孔,不能有效检测出灌装人血白蛋白的注射剂瓶包装阳性对照样品的泄漏;高压放电法可有效避免因药液堵塞漏孔而无法检出泄漏。高压放电法测试电压为9 kV,阈值为15 W,经方法学验证表明,高压放电法具备良好的重复性、中间精密度、准确度和耐用性,泄漏检测限为1 μm。结论: 高压放电法可作为人血白蛋白注射液注射剂瓶包装系统密封完整性的有效考察手段,操作简单,结果真实可靠,且对包装无损,适合商业化产品的包装系统密封完整性检查。
Objective: To establish the research method for the sealing integrity of the injection bottle packaging system for human albumin injection. Methods: For the injection bottle packaging system of human albumin injection, positive control samples with pore diameter of 1 μm were prepared using a glass micropipette, positive control samples with pore diameter of 2, 5 and 10 μm were prepared using laser drilling. Two deterministic sealing integrity testing methods, vacuum decay method and high-voltage leak detection method were developed and tested. Results: The vacuum decay method could not effectively detect the leakage of the packaging system for the human albumin drug preparation due to the blockage of the leakage hole. In contrast, the high voltage leak detection method effectively avoided undetected leakage caused by the blockage of the leakage hole by the liquid medicine. The test voltage was set at 9 kV, with a threshold of 15 W. Methodvalidation demonstrated that the high voltage leak detection method exhibited good repeatability, intermediate precision, accuracy, and durability, with a leakage detection limit of 1 μm. Conclusion: The high-voltage leak detection method can serve as an effective means of inspecting the sealing integrity of the injection bottle packaging system for human albumin injection. The procedure is straightforward, and the results are both accurate and reliable, while also being non-destructive to the packaging. This method is well-suited for the sealing integrity inspection of commercial product packaging systems.
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