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玻璃瓶容器密封完整性测试中的泄漏动态:不同激光钻孔微孔几何形状的影响。

Leakage Dynamics of Glass Bottles on Container Closure Integrity Testing: Influence of Different Laser-Drilled Microhole Geometries.

机构信息

Laser Micro/Nano Fabrication Laboratory, School of Mechanical Engineering, Beijing Institute of Technology, Beijing 100081, China; Beijing Institute of Technology Chongqing Innovation Center, Chongqing 401120, China; Yangtze Delta Region Academy of Beijing Institute of Technology, Jiaxing 314003, China.

Laser Micro/Nano Fabrication Laboratory, School of Mechanical Engineering, Beijing Institute of Technology, Beijing 100081, China; Beijing Institute of Technology Chongqing Innovation Center, Chongqing 401120, China.

出版信息

J Pharm Sci. 2023 May;112(5):1440-1449. doi: 10.1016/j.xphs.2023.01.013. Epub 2023 Jan 24.

Abstract

Container closure integrity testing (CCIT) is a critical step in ensuring package integrity and providing feedback on package designs. In practical applications, CCIT methods, namely physical and probabilistic methods, must be appropriately selected and validated to ensure their suitability for the intended use. However, the industry still lacks practical recommendations regarding the choice of CCIT methods and artificial leaks to set the acceptance criteria. The main reason is the lack of correlation between testing methods. Artificially introduced leak microholes are the only way to determine the sensitivity of a CCIT method and to implement the method correlation. However, the type of artificial leakage is a key factor because in most studies, leakage is described and valued using a single parameter, such as size. This can significantly affect the credibility of the relevant test results, especially in the case of microbial invasion, where the difference in test conditions and samples will severely affect the probability of microbial invasion. Therefore, it is vital to conduct a systematic study on the influence of leakage conditions on CCIT methods. In this study, the influence of the shapes of artificial leaks on the two kinds of testing methods was systematically studied based on a laser-drilled microhole-a highly potential and non-exogenous artificial leak manufacturing method that can fabricate different leakage geometries. The reason for the influence of the shape of an artificial leak on the CCIT is that the deterministic method takes defects as an idealized model and ignores the influence of the leak shape, wall thickness, and other factors on leakage and pollution risks. However, these factors seriously affect the dynamic process of leakage and microbial invasion. The pressure decay method is used to test the leakage flow rate of conical and straight holes. Microbial challenge tests are then used to verify the impact of leakage shapes on the pollution risk. The results of the tests indicated that the probability of microbial invasion in the conical holes is much higher than that in straight holes with the same flow test results and that the wall thickness can also affect microbial invasion. Thus, it can be proven that the risk of leakage and invasion or the sensitivity of different methods cannot only be compared through the leak diameter. Numerous influencing factors, including leakage geometry (e.g., shape and thickness), must be considered in practical applications.

摘要

容器密封完整性测试(CCIT)是确保包装完整性并为包装设计提供反馈的关键步骤。在实际应用中,必须适当选择和验证 CCIT 方法,即物理方法和概率方法,以确保它们适用于预期用途。然而,业界仍然缺乏关于 CCIT 方法和人工泄漏选择的实用建议,以设定验收标准。主要原因是测试方法之间缺乏相关性。人工引入的泄漏微孔是确定 CCIT 方法灵敏度并实施方法相关性的唯一方法。然而,人工泄漏的类型是一个关键因素,因为在大多数研究中,泄漏是使用单个参数(如尺寸)来描述和评估的。这会严重影响相关测试结果的可信度,尤其是在微生物入侵的情况下,测试条件和样本的差异会严重影响微生物入侵的概率。因此,系统研究泄漏条件对 CCIT 方法的影响至关重要。在这项研究中,基于激光钻孔微孔——一种潜在的、非外源性的人工泄漏制造方法,该方法可以制造不同的泄漏几何形状,系统地研究了人工泄漏形状对两种测试方法的影响。人工泄漏形状对 CCIT 产生影响的原因是,确定性方法将缺陷视为理想化模型,忽略了泄漏形状、壁厚等因素对泄漏和污染风险的影响。然而,这些因素严重影响了泄漏和微生物入侵的动态过程。压力衰减法用于测试锥形孔和直孔的泄漏流量。然后进行微生物挑战测试,以验证泄漏形状对污染风险的影响。测试结果表明,具有相同流量测试结果的锥形孔中微生物入侵的概率远高于直孔,壁厚也会影响微生物入侵。因此,可以证明不同方法的泄漏和入侵风险或灵敏度不仅可以通过泄漏直径进行比较。在实际应用中,必须考虑许多影响因素,包括泄漏几何形状(例如,形状和厚度)。

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