Process Design of Continuous Powder Blending Using Residence Time Distribution and Feeding Models

Area of Science:

• Pharmaceutical Engineering
• Chemical Process Development

Background:

• Continuous powder blending is crucial for pharmaceutical manufacturing.
• Process Analytical Technology (PAT) guidelines enhance process understanding and control.
• Optimizing blending of acetylsalicylic acid (ASA) and microcrystalline cellulose (MCC) requires robust process design.

Purpose of the Study:

• To design a continuous powder blending process for ASA and MCC adhering to PAT guidelines.
• To develop in-line monitoring and process control strategies for improved quality assurance.
• To reduce material and instrumental costs associated with process design and implementation.

Main Methods:

• Utilized Near-Infrared (NIR) spectroscopy with multivariate data analysis for in-line monitoring.
• Employed residence time distribution (RTD) models to understand process dynamics.
• Applied designs of experiment (DoE) to assess critical process parameters (CPPs) effects on RTD.
• Developed soft sensor-based process control tools and an operation block model with digital twins.

Main Results:

• Successfully implemented an NIR-based in-line monitoring system.
• Established a deep understanding of process dynamics through RTD modeling.
• Designed effective soft sensors for quality control and material diversion.
• Validated the operational block model for selecting feasible experimental setups.

Conclusions:

• The PAT-based continuous powder blending process design provides deep process understanding and effective quality control.
• The developed soft sensor and digital twin approach significantly reduces costs for process design and implementation.
• This methodology offers a pathway for efficient and cost-effective pharmaceutical powder blending.