In-line particle size measurement based on image analysis in a fully continuous granule manufacturing line for rapid...

Area of Science:

• Pharmaceutical Engineering
• Process Analytical Technology (PAT)

Background:

• Continuous manufacturing offers advantages in pharmaceutical production.
• Implementing Process Analytical Technology (PAT) is crucial for real-time monitoring and control.
• Measuring particle size in high mass-flow granulation processes presents challenges.

Purpose of the Study:

• To demonstrate an in-line PAT tool for rapid process development in continuous powder granulation.
• To introduce a novel method for real-time particle size measurement of high mass-flow regranulated products.
• To validate the performance of the in-line imaging system against established methods.

Main Methods:

• Utilized a continuous powder granulation line including a twin-screw wet granulator, fluid bed dryer, and regranulating mill.
• Developed a new in-line particle size measurement technique using periodic mass flow reduction via a vibratory feeder.
• Employed image analysis for particle size determination, mitigating overlapping issues.
• Investigated the impact of milling settings and liquid-to-solid ratio on particle size.

Main Results:

• The in-line imaging system successfully provided real-time particle size data for high mass-flow materials.
• Particle size measurements correlated well with expected trends and off-line reference data.
• The system demonstrated its capability to monitor the effects of process parameter changes within hours.

Conclusions:

• The developed in-line imaging system is a viable PAT tool for continuous powder granulation.
• Real-time particle size data facilitates rapid process development and enhances quality assurance.
• This technology supports efficient optimization of granulation processes.