Mechanistic modelling of fluid bed granulation, Part I: Agglomeration in pilot scale process

Area of Science:

• Chemical Engineering
• Pharmaceutical Technology
• Process Modeling

Background:

• Fluid bed granulation is crucial for pharmaceutical manufacturing.
• Predicting granulation performance is complex due to interrelated factors.
• Existing models may lack mechanistic correlations to operating conditions.

Purpose of the Study:

• To develop and validate a mechanistic model for fluid bed granulation.
• To correlate model parameters with operating conditions like spray rate and temperature.
• To enable numerical prediction of granule size evolution.

Main Methods:

• Experimental investigation of fluid bed granulation under various conditions.
• Development of a single-compartment, population-balance-based model.
• Model validation against experimental data and correlation of parameters.

Main Results:

• Granule size is strongly interrelated with Loss on Drying (LoD).
• Maximum granule size observed at intermediate LoD; lower LoD yields elongated granules.
• The developed model accurately predicted temporal granule size evolution.

Conclusions:

• The mechanistic model provides reliable predictions for fluid bed granulation.
• Correlating model parameters to operating conditions enhances predictive capabilities.
• This work is a step towards a stand-alone granulation model incorporating heat and mass transfer.