Scaling up of the fluidized bed granulation process

Area of Science:

• Pharmaceutical Engineering
• Chemical Engineering
• Particle Technology

Background:

• Fluidized bed granulation scale-up in pharmaceuticals is often empirical.
• Achieving consistent granule size during scale-up presents significant challenges.
• Existing methods lack a systematic approach for process transfer.

Purpose of the Study:

• To develop a practical and systematic method for scaling up fluidized bed granulation.
• To achieve a target geometric mean granule size of 400 micrometers in scaled-up processes.
• To validate the method across small (5 kg), medium (30 kg), and production (120 kg) scales.

Main Methods:

• Investigated the effect of relative droplet size on granule size in different fluid beds.
• Applied experimental design and developed regression models for scale-up from small to medium scale.
• Utilized relative droplet size and powder bed moisture content as key scaling parameters.

Main Results:

• The effect of relative droplet size on granule size varied between fluid bed systems.
• Regression models successfully predicted granule size for scale-up from small to medium scale.
• Successful scale-up to the production scale was achieved by considering relative droplet size.

Conclusions:

• A systematic approach based on relative droplet size enables predictable fluidized bed granulation scale-up.
• The developed method offers a practical alternative to empirical scale-up in pharmaceutical manufacturing.
• Consistent granule size can be achieved across different scales using this systematic methodology.