Evaluating scale-up rules of a high-shear wet granulation process

Area of Science:

• Pharmaceutical Technology
• Chemical Engineering
• Materials Science

Background:

• High-shear wet granulation is a critical unit operation in pharmaceutical manufacturing.
• Scale-up of granulation processes presents challenges in maintaining consistent granule properties.
• Existing scale-up rules require evaluation for low drug loading formulations.

Purpose of the Study:

• To assess the efficacy of common scale-up rules for high-shear wet granulation.
• To compare granule properties and tablet performance across different scales.
• To identify scale-up strategies for microcrystalline cellulose-lactose formulations.

Main Methods:

• Evaluation of scale-up rules based on impeller speed and wet massing time.
• Characterization of granule properties: particle size, porosity, flow, and tabletability.
• Assessment of tablet dissolution performance across scales.

Main Results:

• Constant tip speed rule resulted in less granulation at larger scales.
• Extended wet massing time compensated for reduced shear at larger scales.
• Constant Froude number and empirical stress rules yielded comparable granule compaction and tablet dissolution.
• Granule porosity correlated with tabletability and dissolution, highlighting its importance in scale-up.

Conclusions:

• Scale-up of high-shear wet granulation requires careful selection of rules to ensure consistent product quality.
• Constant Froude number and empirical stress rules are promising for maintaining granule properties during scale-up.
• Monitoring granule porosity is crucial for predicting tablet performance and optimizing scale-up parameters.