[Quality by design based high shear wet granulation process development for the microcrystalline cellulose]

Area of Science:

• Pharmaceutical Technology
• Chemical Engineering
• Materials Science

Background:

• High shear wet granulation is a critical unit operation in pharmaceutical manufacturing.
• Establishing a robust process requires understanding critical quality attributes (CQAs) and critical process parameters (CPPs).
• Quality by Design (QbD) principles provide a framework for systematic process development and control.

Purpose of the Study:

• To establish and validate the design space for a high shear wet granulation process.
• To identify critical quality attributes (CQAs) and critical process parameters (CPPs) for microcrystalline cellulose granules.
• To enhance process robustness and flexibility through QbD.

Main Methods:

• Utilized Quality by Design (QbD) principles for process development.
• Employed Plackett-Burman design for screening CPPs (e.g., mixing times, speeds, water addition, wet massing, drying time).
• Applied Central Composite Design for optimization and established the design space using polynomial regression models.

Main Results:

• Median granule size and bulk density identified as CQAs.
• Established a validated design space for high shear wet granulation.
• Achieved controlled granule size (250-355 μm) and bulk density (0.4-0.6 g/cm³).
• Models demonstrated good fit (P<0.05) and non-significant lack of fit (>0.1).

Conclusions:

• The established design space enhances the robustness and flexibility of the high shear wet granulation process.
• The QbD approach successfully defined process parameters for consistent granule quality.
• This methodology provides a reliable framework for controlling granule attributes in pharmaceutical manufacturing.