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In the webinar series, we have been discussing various analytical techniques used in the pharmaceutical industry. This month, I wanted to give you a brief review of how CT is used in this industry.

With the advancement of the segmentation and quantitative analysis methods, CT has become an indispensable tool for non-destructive tablet analysis, providing non-destructive 3D views into internal features that were previously hard to characterize.

CT is widely used in both product development and quality control to examine solid dosage forms like tablets and spray-dried and coated particles. Here are some key applications:

Porosity and density distribution

• CT can image and quantify a tablet’s internal porosity (void fraction) and density variations in 3D. Since pores and micro-voids have a good density contrast against the solid material, they are relatively easy to segment.
• The ability to map porosity throughout a tablet is crucial because porosity influences mechanical strength and drug dissolution. For example, higher porosity generally means lower hardness, making tablets more fragile.
• CT studies have shown how compression pressure affects porosity distribution; denser regions and pore networks inside tablets can be visualized and quantified to predict performance. This non-destructive 3D porosity measurement can supplement traditional bulk porosity tests by revealing where in the tablet pores are concentrated. (Characterization of Pharmaceutical Tablets by X-ray Tomography by Vijayakumar et al., https://doi.org/10.3390/ph16050733)
• When there is enough density difference, crystalline and amorphous phases can be segmented and their volume fraction and distribution can be analyzed. (Quantitative Measures of Crystalline Fenofibrate in Amorphous Solid Dispersion Formulations by X-Ray Microscopy, Neilly et al., https://doi.org/10.1016/j.xphs.2020.07.006)
• Furthermore, CT was used to identify aggregations that caused a change in degradation rate. (Pharmaceutical evaluation of atorvastatin calcium tablets available on the Internet: A preliminary investigation of substandard medicines in Japan, Fukami et al., https://doi.org/10.1016/j.jddst.2015.11.006)

Coating thickness and integrity

• CT is ideal to evaluate tablet coatings in 3D. Unlike traditional destructive cross-sectioning or microscopy of a few sample tablets, CT can non-destructively measure the coating thickness uniformity around an entire tablet. By segmenting the low-density coating material from the higher-density core, we can map coating thickness at every point on the tablet surface and compute its distribution.
• This is critical for functional coatings, such as controlled-release or enteric films, where consistent thickness ensures proper drug release. Additionally, CT can detect coating defects such as air gaps, pores, or cracks in the film. High-resolution scans have identified pores or tiny cracks within coatings that could later expand or cause dose dumping. (Characterization of Pharmaceutical Tablets by X-ray Tomography by Vijayakumar et al., https://doi.org/10.3390/ph16050733)
• CT’s value for tablets is well illustrated by a recent formulation study. D’Angelo et al. investigated the effect of aqueous film coating on tablet structure using CT, scanning tablets before and after coating. They found that exposing tablets to water-based coatings caused notable internal changes in porosity. CT images revealed micro-cracks and swelling inside tablets that had been through the aqueous coating process.
• CT provides a holistic 3D view of the construction of tablets. It uniquely complements traditional chemical analyses and often provides crucial insights into formulation development and failure analysis. (Unveiling tablet structural changes: A micro computed tomography analysis of aqueous coating effects, D’Angelo et al., https://doi.org/10.1016/j.ijpharm.2024.125014)

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To learn more about CT application, register for Angela's episode covering CT.👉 Register for the webinar