Resolution and Sensitivity of Inline Focused Beam Reflectance Measurement During Wet Granulation in Pharmaceutically...

Area of Science:

• Pharmaceutical Manufacturing
• Chemical Engineering
• Process Analytical Technology

Background:

• Quality-by-design principles necessitate real-time process monitoring.
• Granule size distribution is a critical quality attribute in drug product manufacturing.
• Inline process analytical technology (PAT) offers advantages for monitoring granulation processes.

Purpose of the Study:

• To evaluate the resolution and sensitivity of inline focused beam reflectance measurement (FBRM) for chord length distribution (CLD) measurement.
• To investigate the impact of process parameters (water addition, impeller tip speed) on inline FBRM measurements.
• To correlate inline FBRM CLD data with offline particle sizing techniques.

Main Methods:

• Utilized a focused beam reflectance measurement (FBRM) C35 probe for inline CLD measurement within a high shear granulator.
• Employed different grades of microcrystalline cellulose (MCC) as model materials.
• Compared inline FBRM data with offline analyses including laser diffraction, microscopy, and sieve analysis.

Main Results:

• Inline FBRM successfully resolved differences in particle size between MCC grades.
• FBRM data showed good correlation with offline particle sizing methods.
• Impeller tip speed influenced the number density of CLD measurements, while water addition reduced CLD, indicating deagglomeration.

Conclusions:

• Inline FBRM CLD measurement offers adequate resolution and reproducibility for monitoring high shear wet granulation.
• This technology is valuable for real-time process monitoring and achieving quality-by-design in pharmaceutical manufacturing.
• FBRM is a robust tool for inline granule size analysis, applicable with and without water present.