Using the Box-Behnken experimental design to optimise operating parameters in pulsed spray fluidised bed granulation

Area of Science:

• Chemical Engineering
• Pharmaceutical Technology
• Process Optimization

Background:

• Fluidised bed granulation is a key process in pharmaceutical manufacturing.
• Controlling granule properties like size and yield is crucial for product quality.
• Optimizing operating parameters requires robust experimental design.

Purpose of the Study:

• To investigate the influence of pulsed frequency, binder spray rate, and atomisation pressure on fluidised bed granulation.
• To develop mathematical models for predicting granule characteristics.
• To determine an optimal design space for the granulation process.

Main Methods:

• Utilized the Box-Behnken experimental design method.
• Developed mathematical models to predict mean granule size, yield, relative width of granule distribution, Hausner ratio, and moisture content.
• Performed validation experiments to confirm model reliability.

Main Results:

• Confirmed that liquid feed pulsing influences granule size.
• Identified a nonlinear quadratic relationship between pulsed frequency and granule size.
• Established a design space for operating parameters based on granule size and yield constraints.

Conclusions:

• The Box-Behnken design is effective for studying fluidised bed granulation.
• Granule size can be controlled via liquid feed pulsing, with careful consideration of frequency.
• The developed models and design space enhance process understanding and optimization.