Tracking raw material flow through a continuous direct compression line Part I of II: Residence time distribution...

Area of Science:

• Pharmaceutical manufacturing
• Chemical engineering

Background:

• Continuous manufacturing (CM) offers superior quality and space-time yield over batch manufacturing.
• High yield losses during CM start-up hinder widespread economic adoption.
• Back-mixing of nonconforming material contaminates subsequent batches, increasing material discharge.

Purpose of the Study:

• To investigate methods for reducing yield losses in continuous manufacturing.
• To identify operational parameters that control the degree of back-mixing.
• To enhance the economic feasibility of CM by minimizing waste.

Main Methods:

• Utilized direct compression methods for process analysis.
• Conducted step-change experiments with color-marked material to quantify parameter impact.
• Developed process models and performed variance-based sensitivity analysis to identify key parameters.

Main Results:

• Identified minimal feeder filling level and tablet press rotational feed frame speed as critical parameters.
• Demonstrated that adjusting these parameters reduces back-mixing by over 30%.
• Quantified the impact of operational parameters on back-mixing and material contamination.

Conclusions:

• Optimizing operational parameters is a simple yet effective strategy to reduce back-mixing in CM.
• Significant reduction in yield loss through parameter adjustment improves CM's economic competitiveness.
• This approach offers substantial savings, particularly with high-cost raw materials.