High-Contrast X-Ray Computed Tomography for Quantifying Amorphous Content in Melt-Quenched Acetaminophen

Area of Science:

• Materials Science
• Pharmaceutical Science
• Analytical Chemistry

Background:

• X-ray computed tomography (XRCT) is used for non-destructive 3D analysis and monitoring structural changes.
• Previous XRCT applications in pharmaceuticals lacked systematic quantitative validation against thermal methods.

Purpose of the Study:

• To evaluate laboratory XRCT for monitoring amorphous pharmaceutical crystallization.
• To validate XRCT's quantitative accuracy using differential scanning calorimetry (DSC).

Main Methods:

• Amorphous content in acetaminophen was quantified using XRCT-based voxel segmentation.
• DSC measured amorphous content via specific heat change at the glass transition temperature.
• Time-dependent crystallization was monitored at 30°C using both XRCT and DSC.

Main Results:

• XRCT showed strong correlation (R² = 0.990) with DSC for quantifying amorphous fraction during crystallization.
• XRCT provided a reliable, voxel-based measure of amorphous content, despite micrometer-scale resolution limits.
• In situ XRCT visualized crystallization initiation and spatial propagation, offering insights beyond bulk thermal analysis.

Conclusions:

• XRCT is a practical and efficient tool for rapid screening of physical stability in early-stage pharmaceutical development.
• The method enables continuous monitoring of a single sample, reducing the number of samples needed.
• XRCT offers valuable information on crystallization behavior, complementing traditional thermal analysis.