Investigation of Quantitative X-ray Microscopy for Assessment of API and Excipient Microstructure Evolution in Solid...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Process Engineering

Background:

• Understanding particle size changes of active pharmaceutical ingredients (API) and excipients during solid dosage form processing is crucial for drug product quality.
• Current methods for in-situ particle analysis during manufacturing are limited.

Purpose of the Study:

• To investigate X-ray microscopy (XRM) as a method for determining in-situ particle size distribution of API and excipients during tablet manufacturing.
• To apply an AI-facilitated XRM image analysis tool for quantitative particle analysis.

Main Methods:

• X-ray microscopy (XRM) was used to analyze API and microcrystalline cellulose (MCC) at various processing stages.
• An artificial intelligence (AI) tool facilitated the quantitative analysis of thousands of individual particles.
• Domain size distributions and component porosity were calculated.

Main Results:

• XRM analysis revealed API agglomerate attrition post-granulation, corroborated by particle size distribution and sieve data showing API fines.
• Changes in MCC particle size distribution were explained by its plastic deformation mechanism.
• Primary MCC particle size distribution remained conserved throughout processing.

Conclusions:

• XRM is a successful, non-invasive method for tracking API and excipient particle properties and microstructure in-process and in final dosage forms.
• The XRM and AI methodology offers a data-rich approach for process understanding and Quality by Design (QbD).