Evaluation of vial crimping integrity using vacuum decay testing and internal pressure monitoring

Introduction
Primary packaging plays a critical role in protecting medicinal products from physical, chemical, and microbiological alterations. Container closure integrity is therefore a critical quality attribute for injectable products, as it ensures sterility maintenance and safe use. Crimp-sealed vials constitute an essential primary barrier; however, crimping defects may remain difficult to detect when integrity loss is only partial. This study aimed to assess vial crimping integrity by detecting potential leaks in rigid, non-porous containers using vacuum-based methods.

Methods
Type I glass vials of 5, 10, and 50 mL, closed with chlorobutyl or bromobutyl stoppers and aluminium caps, were evaluated. Empty or filled vials were placed in a vacuum chamber in which the pressure was reduced to −0.65 bar and maintained for 30 s. Intentional crimping defects were generated by applying insufficient sealing pressure or by creating a lateral incision in the aluminium cap. Chamber pressure variations were monitored using a pressure gauge. In addition, internal vial pressure was measured in a reference vial through a needle connected to the pressure gauge. Pressure variations ≤0.05 bar were considered non-significant under our experimental conditions. Measurements were performed on sets of three vials, with each series repeated three times under identical conditions.

Results
In the absence of an aluminium cap, rapid stopper ejection was observed under vacuum, confirming insufficient mechanical retention. In contrast, inadequately crimped vials showed internal pressure variations of only 0.00–0.01 bar, with no detectable leakage. Following a deep lateral incision, leakage was detected at vacuum levels of −0.34 and −0.48 bar for empty and filled 50-mL vials, respectively.

Internal pressure did not vary significantly in inadequately crimped vials. After introducing a deep and visually detectable lateral defect in the aluminium cap, only empty vials showed significant pressure variations: 0.34 bar for 50-mL vials, 0.43 bar for 20-mL vials, and 0.22 bar for 5-mL vials. No pressure variation was observed for filled vials. No significant difference between chlorobutyl and bromobutyl stoppers was identified under the short-duration test conditions evaluated.

Conclusion
Vacuum decay testing combined with internal pressure monitoring appears to be a robust approach for assessing the closure integrity of rigid, non-porous crimp-sealed vials. Although minor crimping defects were not systematically detected under the tested conditions, major defects resulted in clear loss of container closure integrity. These findings highlight the overall robustness of the stopper–cap system while emphasizing the importance of strict control of the crimping process to ensure the integrity and safety of sterile preparations.