X-ray Microscopic Examination of Pharmaceutical Tablets

Figure 1: Clipped Maverick Indie rendering of a zinc tablet, colorized based on local density

Micro-CT is an established method for quality control and formulation development in the pharmaceutical industry. The use of micro-CT for quality inspection and improvement emphasizes its capacity to evaluate dimensional information. With its ability to improve product quality, reduce inspection and analysis costs, and decrease manufacturing time to market, micro-CT is used to accelerate drug development and inspection and gain better insight of defects in manufacturing, as well as to verify packing and coating integrity.

We utilized the SkyScan 1272 desktop micro-CT to identify and quantify the distribution of the metal salt-containing regions of the tablet as an assessment of the distribution of ingredients in the final finished dosage form of the supplement.

X-Ray Microscopic Imaging of Pharmaceutical Tablets

An over-the-counter zinc supplement was mounted in a low-density plastic tube for imaging. The goal of the study was to examine the three-dimensional volume of the tablet to ensure a heterogeneous distribution of active ingredients throughout the tablet.

We examined the tablet using our high-resolution SkyScan 1272 micro-CT with an isotropic voxel size of 8.5 µm. With a high-resolution scientific CMOS camera, the SkyScan 1272 is a great match for pharmaceutical tablets and raw materials.

Figure 2: Planar 2D slices through the zinc supplement tablet

As shown in Figure 2, DataViewer provides us with a linked set of 2D images to navigate through the dataset. These views allow us to interactively move through each dataset for comparative purposes. Within the volume of the tablet, we observe large, dense regions that are likely to primarily contain the active ingredient, zinc gluconate. A small amount of calcium and magnesium are also present, which could also elevate the local density observed in the dataset.

In micro-CT imaging, the higher an element’s atomic number, the higher the X-ray attenuation by that element in our data, which results in areas of increased brightness in our reconstructed datasets. Of the ingredients in the tablet, zinc is the primary active ingredient and the most prevalent. Zinc is also the densest ingredient based on its atomic number as a transition metal. The other ingredients, calcium and magnesium, are alkali earth metals.

Figure 3: Clipped CTVox rendered volumetric representation of the zinc tablet showing the distribution of denser components within the center core of the imaged tablet

Using CTVox, we virtually sliced into the tablet to explore the three-dimensional distribution of ingredients, as shown in Figure 3. The bright regions are primarily composed of zinc with some minor contributions from magnesium and calcium; the darker regions are organic in nature and consist of binding and stabilizing agents.

 

Figure 4: Quantitative assessment of local thickness of low density (organic) and higher density (inorganic) components within the tablet dataset

Using CTAnalyzer, we applied global thresholds to segment either the low-density materials or the higher-density materials to calculate the thickness of the materials in 3D space as a function of the total volume of said material, as shown in Figure 4. Aligning well with our qualitative view of the tablet, most of the lower density materials, which are primarily organic and comprise about 27% of the overall tablet volume, were thin with an average thickness of 114 ± 43 µm. The larger, denser materials comprised the remainder of the tablet volume and were found to have an average thickness of 264 ± 142 µm.

Using CTAnalyzer, we applied global thresholds to segment either the low-density materials or the higher-density materials to calculate the thickness of the materials in 3D space as a function of the total volume of said material, as shown in Figure 4. Aligning well with our qualitative view of the tablet, most of the lower density materials, which are primarily organic and comprise about 27% of the overall tablet volume, were thin with an average thickness of 114 ± 43 µm. The larger, denser materials comprised the remainder of the tablet volume and were found to have an average thickness of 264 ± 142 µm.

Figure 5: Clipped CTVox rendered representation of the quantitative data highlighting the location of both the higher-density materials (magenta) and the low-density materials (blue)

If we take the quantitative size data obtained from CTAnalyzer, we can overlay each component within CTVox, as shown in Figure 5. This clipped view once again highlights the distribution of materials within the center core of the tablet with added color context to help differentiate the denser materials from the lighter materials.

Figure 6: Clipped Maverick Indie rendered representation of the quantitative models highlighting the location of both the higher-density materials (magenta) and the low-density materials (purple)

After creating independent 3D models for both the lower and higher-density materials within the tablet, a clipped view showing the distribution of both material groupings was rendered, as shown in Figure 6.

Conclusion

Among the SkyScan product line, the SkyScan 1272 is a key tool within many laboratories with a great balance between resolution and imaging time. As the highest-resolution desktop model available within the SkyScan portfolio, the SkyScan 1272 is a great match for imaging pharmaceuticals, organic structures, and ceramics. The ability to add a 16-position sample exchanger helps to maintain high throughput for large imaging studies of samples.

We hope you found this Image of the Month informative and encourage you to subscribe to our newsletter and social media channels in preparation for the continuation of our Image of the Month series next month.

Scan Specifications

Sample Zinc Supplement Tablet
Voltage (kV) 90
Current (µA) 111
Filter Aluminum + Copper
Voxel Size (nm) 8.5
Rotation Step 0.3
Exposure Time (ms) 1194
Rotation Extent (deg.) 360
Scan Time (HH:MM:SS) 02:12:29

These scans were completed on our SkyScan 1272 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 identified regions of higher and lower density within the tablet were converted to separate 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.

*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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