Tablet diversion strategy based on in-line NIR tablet press feed frame measurements

Area of Science:

• Pharmaceutical Manufacturing
• Process Analytical Technology (PAT)
• Spectroscopy

Background:

• Traditional sampling methods for oral solid dose manufacturing are interval-based and less efficient.
• Real-time monitoring enhances process understanding and compliance in batch and continuous manufacturing.
• Near-infrared (NIR) spectroscopy is a key Process Analytical Technology (PAT) for in-line blend uniformity analysis.

Purpose of the Study:

• To evaluate a tablet diversion strategy using in-line NIR measurements for real-time blend uniformity monitoring.
• To link in-line blend uniformity data with tablet content uniformity for effective process control.
• To predict API content in tablets based on feed frame NIR measurements, minimizing yield loss.

Main Methods:

• In-line NIR blend uniformity measurements in the tablet press feed frame.
• Off-line Raman tablet content uniformity measurements.
• Tank-in-series (TIS) modeling to derive Residence Time Distribution (RTD) between measurement points.
• Evaluation of spectral loss impact on PAT sensor auto-correction.

Main Results:

• The study successfully predicted API content in tablets using in-line NIR feed frame measurements.
• The derived RTD allowed accurate prediction of tablet content from blend uniformity data.
• The strategy effectively avoids yield loss by only diverting non-compliant batches.
• Spectral loss due to auto-correction was evaluated, identifying conditions for potential deviation detection.

Conclusions:

• The tablet diversion strategy, utilizing in-line NIR blend uniformity, is a viable approach for pharmaceutical manufacturing.
• This PAT-based strategy enhances real-time monitoring and control, improving process efficiency and compliance.
• Diversion failures are highly unlikely under normal operating conditions, ensuring reliable process control.