Evaluation of a container closure integrity test model using visual inspection with confirmation by near infra-red...

The objective of this study was to evaluate a novel test model involving an easy and rapid method to assess parenteral container/closure integrity. In this study, an extremely hygroscopic powder (methacholine chloride) was filled into the test vial/closure combination and served as an indicator of water vapor ingress into the package through either the stopper/glass interface and/or permeation through the closure. A visual means of detection was used initially, as the powder liquefies upon contact with a high-humidity environment. A further level of sensitivity was gained by using Near Infra-Red (NIR) spectroscopy to confirm that no additional water vapor was detectable in the test vials after being subjected to autoclave (worst-case water ingress) treatments. After two sequential autoclave cycles, none of the samples in the pilot study showed liquification of the indicator powder. This indicated that there was negligible ingress of water vapor, and therefore, the container/closure combination provided an adequate barrier to moisture ingress at the stress temperature and pressure conditions studied. The sensitivity of the NIR water ingress detection method was shown to be in the range needed for an acceptable vial integrity test. In conclusion, the model evaluated in this study can be used as an easy, rapid, and non-destructive closure integrity evaluation test. The use of such a NIR spectroscopy method would be immediately and directly amenable to the evaluation of vial integrity of dry powder-filled and lyophilized products, or can be used indirectly as shown in this study to assess container closure integrity for liquid-filled parenteral vial closure systems.