Multiscale X-ray imaging and characterisation of pharmaceutical dosage forms

Area of Science:

• Materials Science
• Pharmaceutical Sciences
• Advanced Imaging Techniques

Background:

• Solid dosage form performance is critically dependent on drug morphology and solid-state phase.
• Understanding structure-property relationships requires multiscale characterization from nanometers to millimeters.
• Current imaging techniques often lack the resolution or scale to fully capture complex solid dosage form structures.

Purpose of the Study:

• To present a correlative, multiscale imaging methodology for visualizing and quantifying the morphology of solid dosage forms.
• To establish a workflow for multiscale analysis, bridging nanometer to millimeter scales.
• To demonstrate the methodology's capability in characterizing drug morphology and solid-state phase in a specific pharmaceutical formulation.

Main Methods:

• Combining ptychographic X-ray computed nanotomography (PXCT) for 3D morphology visualization at 80 nm resolution.
• Utilizing scanning small- and wide-angle X-ray scattering (S/WAXS) for nanostructure and polymorphic form analysis.
• Applying the integrated methodology to a hot-melt extruded solid dispersion of carbamazepine in ethyl cellulose.

Main Results:

• PXCT revealed an oriented 3D morphology of crystalline drug domains aligned with the extrusion direction over extended volumes.
• S/WAXS indicated consistent nanostructure across the extruded filament's cross-section, with minor radial variations in domain size and orientation.
• WAXS identified a heterogeneous distribution of metastable carbamazepine forms I and II within the solid dispersion.

Conclusions:

• The developed multiscale imaging methodology enables comprehensive structural characterization of solid dosage forms.
• This approach enhances understanding of the intricate relationships between morphology, processing, and performance.
• The findings provide a foundation for optimizing pharmaceutical formulations through detailed structural insights.