In situ wet pharmaceutical granulation captured using synchrotron radiation based dynamic micro-CT

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Imaging Techniques

Background:

• Wet granulation is a key pharmaceutical process for producing tablets and capsules.
• Granule microstructure significantly impacts final product performance.
• Traditional imaging methods are too slow to capture dynamic granulation events.

Purpose of the Study:

• To demonstrate the capability of synchrotron radiation-based dynamic micro-computed tomography (micro-CT) for studying wet granulation.
• To investigate the evolving internal microstructure of pharmaceutical granules during the granulation process.
• To provide quantitative insights into early-stage wet granulation dynamics.

Main Methods:

• Utilized synchrotron radiation-based dynamic micro-CT for high-speed, non-destructive imaging.
• Employed lactose monohydrate (LMH) as a model powder for wet granulation experiments.
• Applied phase-retrieval algorithms to enhance image contrast and enable detailed analysis.

Main Results:

• Successfully captured the rapid microstructural evolution during LMH wet granulation (seconds timescale).
• Observed and quantified granule consolidation and the dynamic changes in internal porosity.
• Determined the influence of particle aggregates on the evolving granule porosity.

Conclusions:

• Synchrotron-based dynamic micro-CT is a powerful tool for real-time analysis of fast processes like wet granulation.
• This technique offers significant advantages over 2D and ex situ methods for understanding granule formation.
• The study provides crucial insights into the microstructural development influencing pharmaceutical granule quality.