Spatial and Temporal Visualization of Polymorphic Transformations in Pharmaceutical Tablets

Area of Science:

• Materials Science
• Pharmaceutical Science
• Analytical Chemistry

Background:

• Non-destructive analysis is crucial for pharmaceutical tablet characterization.
• Understanding material transformations under compression is vital for manufacturing.
• X-ray Diffraction Computed Tomography (XRD-CT) offers molecular-level insights with spatial resolution.

Purpose of the Study:

• To apply XRD-CT for analyzing pharmaceutical tablets under varying compression pressures.
• To investigate pressure-induced transformations of a glycolide marker within tablets.
• To study the temporal changes, including hydrolysis, of tablet components.

Main Methods:

• Application of X-ray Diffraction Computed Tomography (XRD-CT) to pharmaceutical tablets.
• Utilizing a pressure-sensitive glycolide marker to track compression effects.
• Conducting follow-up analysis after one month to observe in situ reactions.
• Employing electron diffraction for structural elucidation of hydrolysis products.

Main Results:

• XRD-CT successfully revealed material changes within tablets without destruction.
• Pressure-induced transformations of glycolide were pinpointed within the tablet structure.
• An in situ hydrolysis reaction of glycolide was observed one month post-compression.
• The structure of the glycolide hydrolysis product was determined using electron diffraction.

Conclusions:

• XRD-CT is a powerful tool for non-destructive analysis of pharmaceutical tablet manufacturing processes.
• The study demonstrated the ability to track dynamic material changes and reactions within tablets over time.
• Understanding these transformations is key to optimizing tablet quality and stability.