RTD-based material tracking in a fully-continuous dry granulation tableting line.

Area of Science:

• Pharmaceutical Manufacturing
• Chemical Engineering
• Process Analytical Technology (PAT)

Background:

• Continuous manufacturing (CM) presents advantages over traditional batch processing.
• Material traceability is crucial for CM but challenging to implement.
• Existing methods lack robust traceability solutions for integrated CM lines.

Purpose of the Study:

• To develop and validate a process model for material traceability in continuous dry granulation.
• To assess the predictive capability of residence time distribution (RTD) models for CM.
• To demonstrate the utility of process simulation in pharmaceutical CM development.

Main Methods:

• Residence time distributions (RTD) were measured using NIR spectroscopy for individual unit operations (blender, roller compactor, tablet press).
• RTD models were developed using transfer functions for continuous operations and frequency-based assumptions for semi-continuous ones.
• A step change in API was simulated and experimentally validated across the entire manufacturing line.

Main Results:

• The developed RTD models accurately predicted material propagation through the continuous dry granulation line.
• The process simulation demonstrated strong predictive power at selected mass flow rates.
• Experimental validation confirmed the model's effectiveness for traceability in a complete CM line.

Conclusions:

• Process simulation, utilizing RTD models, is a powerful tool for developing and controlling continuous pharmaceutical manufacturing.
• This approach enhances material traceability, a key requirement for CM implementation.
• The study validates a novel method for ensuring process understanding and control in pharmaceutical CM.