Static and in-situ synchrotron X-ray microtomography analysis of pharmaceutical tablets

Pharmaceutical solid dosage forms are designed to control drug release timing and location in the body, ranging from immediate-release to delayed-release formulations such as enteric-coated tablets. Ensuring content uniformity, consistent dissolution, and intact excipients is vital for their efficacy and safety. Manufacturing flaws - like defective coatings, cracks, or porosity - can compromise performance, making precise quality control essential. X-ray computed microtomography (µCT) enables non-destructive assessment of internal morphology, coating thickness, porosity, active ingredient distribution, and density. However, conventional laboratory µCT systems may lack the resolution, sensitivity, or speed required for advanced dynamic structural analysis. Synchrotron radiation-based µCT (SR-µCT) addresses these limitations, offering significant improvements in spatial resolution and temporal performance. This paper highlights the capabilities of SR-µCT for (i) high-throughput structural analysis and (ii) time-resolved monitoring of the dissolution of solid dosage forms. A commercially available pantoprazole tablet serves as a case study to demonstrate the tradeoff between resolution and field-of-view. Structural analysis of this pantoprazole tablet includes porosity and coating thickness quantification, as well as detection of morphological defects at different voxel sizes. Additionally, a newly developed flow-through chamber which allows liquid from a 100 ml reservoir to circulate and renew during measurements is presented for dynamic disintegration studies under sink conditions. Fast dynamic time-resolved SR-µCT analysis shows the disintegration speed of multicomponent placebo formulation compacted tablets at rapid µCT tomogram recording times of 5 s, while (high-resolution) time-resolved SR-µCT captures swelling in sustained-release formulations (Beloc Zok), API (size) distribution as well as API shape distribution.