Scale-up feasibility in high-shear mixers: determination through statistical procedures

Area of Science:

• Pharmaceutical Technology
• Chemical Engineering
• Materials Science

Background:

• Wet granulation is a critical unit operation in pharmaceutical manufacturing.
• Scale-up of wet granulation processes can be challenging due to variations in process parameters.
• Understanding formulation behavior under compression, such as plastic deformation, is crucial for successful scale-up.

Purpose of the Study:

• To examine the wet granulation scale-up of a formulation exhibiting plastic deformation.
• To investigate the effects of solution level, mixing time, and mixer speed on granulation properties.
• To assess the robustness of a microcrystalline cellulose and pregel starch excipient system during scale-up.

Main Methods:

• Experimental factorial design was employed to study the impact of key process parameters.
• Granulation properties including mean particle size, density, Carr's index, and flow rate were measured.
• Tablet hardness was evaluated for formulations produced under different granulation conditions.

Main Results:

• Granulation characteristics were highly reproducible across different process conditions.
• The microcrystalline cellulose and pregel starch formulation demonstrated resistance to scale-up variations.
• Tablet hardness remained consistent, indicating formulation stability.

Conclusions:

• The microcrystalline cellulose and pregel starch excipient system is robust for wet granulation scale-up.
• The formulation's plastic deformation behavior contributes to its reproducibility and resistance to process changes.
• This finding supports the use of this excipient system in high-shear mixer scale-up operations.