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Simpleware Case Study: Understanding the Stopper Sealing Process for Parenteral Vial Integrity
Overview
The most common closure system used to seal glass vials containing parenteral pharmaceuticals is an elastomer stopper held in place by a crimped aluminum band. This closure system is used to protect the contents against environmental factors including microbial contamination. X-ray micro-computed tomography (micro-CT) can provide detailed information regarding the position of the elastomer stopper and aluminum band both before and after the sealing process of parenteral vials. This information can be used to evaluate the closure integrity and identify if changes need to be made to the sealing process to ensure the integrity of the seal. Synopsys Simpleware software was used to accurately model and analyze the micro-CT data as part of a joint project with Micro Photonics.
Highlights:
- X-ray CT data enables close study of vial integrity
- Simpleware software enables extensive image processing, segmentation, and surface deviation analysis of cap deformation
- Project opens possibility for wider analysis of different vial capping scenarios
Thanks to:
Seth Hogg, Benjamin Ache, ,
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.
High Resolution micro CT scans of parenteral vials at the two different stages of the sealing process. The scan on the left shows the open configuration, the scan on the right the closed configuration.
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.
Segmented vial in the open configuration with the aluminum seal in place (left) and with the aluminum seal hidden to show the uncompressed stopper (right), created using Simpleware software.
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.
A) Deformed stopper cross section (green) overlaid on open stopper (red) and vial cross section; B) Deformed aluminum seal cross section (green) overlaid on open seal (red) and vial cross section; C) Stopper and seal in the open configuration; D) Stopper and seal in the closed configuration. Measurements taken as shown indicate that there is a 22% compression of the cap when the closed configuration is compared to the open configuration.
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.
A) Deformed stopper from the closed configuration (translucent green) overlaid on the open stopper (red); B) C) and D) color maps illustrating the deformation of the closed stopper using the open stopper as the reference surface.
The data obtained also revealed that the deformation (crimping) of the aluminum band was not uniform.
Underside of the metal sealing band open configuration (left), and closed configuration (right). Note the non-uniformity of the crimping in the closed configurations.
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.
Any Questions?
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