X-ray Microscopic Examination of Multilayer Tablets

Figure 1: Photograph of the multilayer tablet

The simplicity and large-scale manufacturing capabilities of pharmaceutical tablets are key to their wide usage for drug administration. Micro-CT high resolution 3D visualization is indispensable as a non-destructive technique to investigate the internal structure of tablets, for both product development and production quality control. Full-tablet imaging provides porosity analysis, crack and delamination analysis, and volumetric calculations. We utilized the SkyScan 1275 desktop micro-CT to qualitatively and quantitatively explore a multilayer tablet and assess the native contrast within the sample between the different components.

X-Ray Microscopic Imaging of Pharmaceutical Tablets

To simulate a multilayer pharmaceutical tablet, we imaged a multilayered breath freshening product obtained from a local grocer. We examined the tablet using our high-speed SkyScan 1275 micro-CT at an isotropic voxel size of 10 µm. The SkyScan 1275 is a fine match for this project due to its quick sample collection for organic materials such as the formulations used for many pharmaceutical products. The ability to operate the SkyScan 1275 using a push-button imaging sequence start command allows the instrument to serve well in a quality control role as well for small batches of samples removed from larger production runs.

Figure 2: Planar 2D slices through the tablet

As shown in Figure 2, DataViewer provides us linked views through the overall shape and distribution of the formulated product ingredients. As we click any individual particle or pore in the dataset, the other two views respectively change to center upon the clicked location. From this view, we see a variety of particles and pores present within the tablet. However, we do not see any delineation in the dataset between the pink layer and the white layer. Thus, without native contrast in the sample, we would be unable to quantitatively draw any conclusion related to specific features of either half of the tablet. Instead, our quantitative output would be inclusive of the entire tablet.

Despite the two halves of the tablet being visually different to our eye, micro-CT imaging relies on differential X-ray attenuation through the sample to provide contrast in the reconstructed datasets we interact with. In this case, both the white portion of the sample and the pink portion of the sample must therefore attenuate X-ray energy similarly. This is logical if the primary difference between the two halves of the tablet is based on the addition of a pink organic pigment to the colored half of the tablet. Since the primary composition of the tablet is organic, the addition of a pink organic dye to a portion of the sample would not produce any additional contrast in this region of the sample, as the sample remains primarily organic in composition. In most cases, micro-CT imaging does not provide elemental data for samples and thus cannot determine differences between compounds of similar composition.

Figure 3: Clipped rendered volumetric model from CTVox along the center axis of the tablet

Continuing what we observed from DataViewer, CTVox allows us to explore the tablet as a full volumetric model as shown in Figure 3. Once again, we cannot observe any differences between the white and pink halves of the tablet.

Figure 4: Clipped 3D view in CTVox of the sphere fitting models from CTAn overlaid onto the dataset colorized to highlight pores (red) and denser inclusions (blue)

CTVox allows us to visualize the quantitative structural data as shown in Figure 4. In this view, we first overlaid the porosity data obtained from CTAn and subsequently overlaid the thickness data from the denser inclusions to create a three-tiered dataset.

Figure 5: Calculated pore diameters within the tablet volume

As shown in Figure 5, a normal distribution focuses upon our pore diameters. The average pore was determined to be 67.5 ± 37.8 µm with a total porosity of less than one percent.

Figure 6: Maverick 3D renderings of whole dual layer tablet (top and dense sphere diameter analysis colorization (bottom)

From our reconstructed datasets and CTAn output files, we were able to import different versions of our dataset into Simpleware ScanIP software with the CAD add-on module to segment into volumetric models. Maverick Render Indie then allowed us to apply colors and textures to the models as shown in Figure 6.

Conclusion

Among the SkyScan product line, the SkyScan 1275 is a workhorse high-speed instrument which excels with imaging and analysis of both organic and inorganic samples. The small footprint and full self-shielding make the SkyScan 1275 a great fit for most laboratories and some quality control processes.

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Scan Specifications

Sample Breath Freshening Tablet
Voltage (kV) 80
Current (µA) 125
Filter 1 mm aluminum
Voxel Size (nm) 10
Rotation Step 0.3
Exposure Time (ms) 165
Rotation Extent (deg.) 360
Scan Time (HH:MM:SS) 01:07:10

These scans were completed on our SkyScan 1275 micro-CT system at the Micro Photonics Imaging Laboratory in Allentown, PA. Reconstructions were completed using NRecon 2.0 while visualization and volumetric inspection of the 2D and 3D results were completed using DataViewer and CTVox. The tablet and individual components were converted to STL volumetric models using Synopsys’ Simpleware ScanIP software with the CAD add-on module (Synopsys, Inc., Mountain View, USA) before 3D rendering using Maverick Render Indie (Random Control, Madrid, Spain).

Would you like your work to be featured in our monthly newsletter? If so, please contact us by calling Seth Hogg at 610-366-7103 or emailing seth.hogg@microphotonics.com.

References

*Simpleware software (Synopsys, Inc., Mountain View, USA) enables you to comprehensively process 3D image data (MRI, CT, micro-CT, FIB-SEM…) and export models suitable for CAD, CAE and 3D printing. Use Simpleware software’s capabilities to visualize, analyze, and quantify your data, and to export models for design and simulation workflows. Simpleware™ is a trademark of Synopsys, Inc. in the U.S. and/or other countries.

 

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