X-ray Microscopic Inspection of Counterfeit Pharmaceuticals

Figure 1: Photograph of known (left) and questioned (right) capsules

Pharmaceutical counterfeits impact the intellectual property of the originator of the drug but also undermine the safety of the public. Because counterfeit drugs often contain only small amounts of the active ingredient, they can abate some symptoms but not fully cure or treat disease and may contribute to drug-resistant strains.

Larger pharmaceutical companies often have entire forensic teams dedicated to investigating illegal products. Micro-CT is highly suited for forensic investigations of pharmaceutical tablets and capsules with its non-destructive quantitative view within samples, readily allowing for the comparison of known and questioned samples. In this work, we simulated a forensic investigation by comparing a brand name product to a generic equivalent. Our simulated scenario focuses on the exploration of the hidden inner contents and composition of these two capsules rather than the outside surfaces, which in this case do have visible physical differences.

X-Ray Microscopy Imaging of Counterfeit Pharmaceutical Products

For our article this month, we chose to focus on imaging these pharmaceutical tablets using the SkyScan 1272 high resolution desktop micro-CT. As can be seen from the view in Figure 1 above, both samples are relatively similar in outward surface appearance. However, micro-CT examination allows for the comparison of internal features and structures without compromising sample integrity. 

Figure 2: Planar views of reconstructed data from the known (top) and questioned (bottom) tablets

As shown in Figure 2, the SkyScan 1272 immediately demonstrated a major difference between the samples which was not outwardly apparent by initial inspection. Namely, the questioned tablet’s outermost coating is merely stretched around the inner coated tablet, leaving air voids at both ends of the tablet. The known tablet conversely has the outermost coating applied directly to the inner coated tablet with no air voids visible in the tablet construction.

Figure 3: Volumetric rendering of inner tablet coating thickness for the known (top) and questioned (bottom) samples

After discovering the significant differences between the two samples regarding the outermost coatings, the investigation next moved to the highly attenuating coating applied to the inner tablets. This inner coating is the highest density component of both tablets, so it makes for another good point of comparison. After segmenting the coating in both samples using a global threshold, a structure thickness analysis within CTAn produced a color-coded map of coating thickness in 3D space (Figure 3). Both images in the figure are mapped onto the same color scale where thinner regions are in blue and thicker regions are shown in red. The known sample presents a thicker coating in the interface between the central band and the two tablet domes than is observed in the questioned sample.

Figure 4: Calculated inner tablet coating thickness distribution

The volumetric images of inner tablet coating thickness can also be converted to a quantitative plot of calculated coating thickness as a fraction of the total coating volume identified in Figure 4. While not yet conclusive with such a small sampling, a difference in coating thickness does appear likely based on these early results. The average thickness of the known sample coating was determined to be 51.8 µm while the same coating was found to only be 36.2 µm in the questioned sample, a 30% reduction. To further define a difference between the known and questioned samples, additional known samples should be analyzed to determine where the thickness of the questioned sample’s inner tablet coating falls amongst the natural manufacturing variability of the known tablets.


The SkyScan 1272 allowed us to non-destructively compare a known pharmaceutical sample to a questioned sample. This comparison highlighted several key differences internal to the sample and not visible upon external examination. 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

Voltage (kV)60
Current (µA)166
Pixel Size (µm)4
Rotation Step0.2
Scan Time (HH:MM:SS)05:09:44

These scans were completed on our desktop SkyScan 1272 system at the Micro Photonics Imaging Laboratory in Allentown, PA. Reconstructions were completed using NRecon and visualization of 2D and 3D results were completed using DataViewer, CTVox, and CTAn.

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 e-mailing seth.hogg@microphotonics.com.

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