Soft sensor for real-time estimation of tablet potency in continuous direct compression manufacturing operation

Area of Science:

• Pharmaceutical Manufacturing
• Process Analytical Technology (PAT)
• Quality by Design (QbD)

Background:

• Tablet potency is a critical quality attribute in solid oral dosage forms produced via continuous direct compression.
• Real-time monitoring of potency and excipient concentrations is essential for process control and product quality.

Purpose of the Study:

• To develop and validate a novel soft sensor for real-time monitoring of blend and tablet potency.
• To enable flexible manufacturing through a product-agnostic soft sensor model.

Main Methods:

• A hybrid soft sensor model combining first-principle and empirical approaches was developed.
• The model incorporates minimal adjustable parameters tied to equipment design and operation.
• Real-time experiments assessed model accuracy during steady-state and dynamic process transitions.

Main Results:

• The soft sensor accurately estimated tablet potency in real-time, validated against offline analytical testing.
• The model demonstrated robustness in monitoring both steady-state and dynamic potency variations.
• The product-agnostic nature of the sensor facilitates its application across different pharmaceutical products.

Conclusions:

• The developed soft sensor is a reliable tool for real-time potency monitoring in direct compression.
• The soft sensor can be integrated into control strategies for product diversion and advanced process control.
• This technology supports minimizing tablet composition variability and enhancing manufacturing efficiency.