Formulation design for optimal high-shear wet granulation using on-line torque measurements

Area of Science:

• Pharmaceutical Technology
• Chemical Engineering
• Materials Science

Background:

• High-shear wet granulation is a critical unit operation in pharmaceutical manufacturing.
• Controlling granule growth is essential for achieving desired drug product performance.
• Existing formulation design methods often lack precision in predicting granulation behavior.

Purpose of the Study:

• To develop an alternative procedure for formulation design in high-shear wet granulation.
• To propose a novel formulation map that describes the onset of significant granule growth.
• To establish a method for predicting the minimum liquid binder volume required for granulation.

Main Methods:

• Monitoring granule growth using on-line impeller torque measurements.
• Evaluating granule growth via changes in granule particle size distribution.
• Constructing the formulation map using binder glass transition temperatures and static humidity conditioning.

Main Results:

• The onset of granule growth is indicated by an abrupt increase in impeller torque.
• A 'minimum liquid volume' threshold was identified, dependent on binder and diluent properties.
• The formulation map successfully correlates formulation variables with granule growth onset.

Conclusions:

• The proposed formulation map provides a predictive tool for optimizing high-shear wet granulation.
• Understanding the minimum liquid volume is key to controlling granule size and process outcomes.
• This approach enhances formulation design by linking material properties to granulation behavior.