Simpleware Case Study: Understanding the Stopper Sealing Process for Parenteral Vial Integrity

Image Acquisition

High resolution X-ray micro-CT scans were obtained for two separate vials that were removed from the production line prior to and after the sealing process was completed. The first vial represents the open configuration in that the elastomer stopper and aluminum band are in place; however, the aluminum band has not been crimped and the stopper is uncompressed. The second vial represents the closed or sealed configuration in which the aluminum band has been fully crimped thereby compressing the stopper to seal the vial.  The imaging was done on a Bruker SkyScan 1275 Micro-CT and the projections were reconstructed as serial sectioned images having an isotropic voxel size of 25 microns.

Image Processing / Segmentation

The images from each vial were imported into the  Simpleware ScanIP Software environment as a stack of bitmap images. The vial, stopper and seal were segmented for both configurations using a combination of thresholding, morphological filters and 3D editing tools. A smoothing filter was applied to the segmented data to smooth the surfaces prior to further processing.

Characterization of the Sealing Process

The segmented stopper and band from both vial configurations were converted into Stereolithography surface (STL) objects and imported into a project file containing the image data of the open vial configuration for comparison purposes. Using the Simpleware CAD module, a surface deviation analysis was performed to quantify the deformation of the stopper in the closed configuration by comparing it to the stopper in the open configuration. The surface deviation process involved registering the stopper surface in contact with vial top in the closed configuration with the equivalent surface on the stopper from the open configuration.

Surface deviation was measured by using the open stopper as the reference surface and measuring the distance from sampling points on the open stopper to the nearest point on the deformed stopper. The measured distances were then displayed as a color map on the reference stopper. Simpleware ScanIP was also used to visualize the deformation of the aluminum band during the sealing process by overlaying the deformed band onto the images of the original open band. The band was also registered to the vial surfaces and images showing the overlap of the closed band relative to the open band were created to visualize the deformation.

Results

Overlaying of the deformed stopper onto the image of the open stopper and vial provided qualitative information regarding how the stopper deforms during the sealing process. The top part of the stopper is compressed.  This causes the stopper to deform laterally over the top surface of the vial and lip over the vial edges. The portion of the stopper that is located within the vial neck can be seen to be forced downward into the vial during the sealing process.

The surface deviation map in Simpleware software quantifies the deformations. The lateral deformation of the stopper wall as well as the downward deformation of the stopper top and movement of the bottom of the stopper into the vial are observed and quantified. The maximum deformation of the stopper was 1.07 mm.  The regions of greatest deformation corresponded to the top of the stopper.  It was observed that lateral deformations of the sidewalls of the stopper were not uniform with maximal lateral deformations being concentrated on one side of the stopper.

The data obtained also revealed that the deformation (crimping) of the aluminum band was not uniform.

This case study illustrates a method to non-destructively quantify and evaluate the deformation of an elastomer cap and sealing band during the sealing process of a parenteral vial. Additional work will need to be done to correlate the deformation values to the actual sealing quality of the vial. To further develop this model, additional testing would be required with vials closed under different vial capping machine settings. These additional samples should also undergo traditional container closure integrity testing to compare to results identified using the methods described in this manuscript. By correlating these results, it would be possible to obtain a better understanding of how stopper and band deformation during the sealing process affect the integrity of the seal.