Inline moisture analysis in a pilot scale granulation process by NIRS

Importance of Topic

Proper control of residual moisture during top-spray granulation is vital for pharmaceutical production. Incorrect moisture levels can lead to particle fracture, caking, and downstream processing issues. Inline monitoring of moisture content provides real-time data that supports optimal process control, reduces waste, and improves product quality.

Objectives and Study Overview

This application demonstrates the use of near-infrared spectroscopy (NIRS) for inline moisture analysis in a pilot-scale fluid bed granulation process. The study evaluates how the Metrohm Process Analytics NIRS Analyzer PRO, equipped with a dedicated fluid bed probe, can track moisture content in real time and inform end-point decisions for the drying cycle.

Methodology

• Top-spray granulation of a powder blend in a fluid bed dryer, with a liquid binder sprayed onto the fluidized bed.
• Inline spectral acquisition in the 1100–1650 nm range using a micro-interactance probe mounted directly in the dryer.
• Automated air purge after each measurement to clear the probe tip and ensure consistent sampling.
• Calibration against laboratory reference moisture methods across a 0–60 % range to build robust NIRS models.

Instrumentation Used

• NIRS Analyzer PRO – FiberSystem (A629281120): High-resolution diode array spectrometer for nondestructive reflectance and transflectance measurements via fiber-optic microbundles.
• Micro-interactance reflectance probe with a ‘spoon’ tip and purge ports: Designed for direct insertion into fluid bed dryers to maintain consistent powder contact and prevent buildup.

Key Results and Discussion

• Real-time moisture trend: The NIRS system tracked moisture decline over time, displaying an asymptotic approach to the target moisture level.
• Improved end-point determination: Operators used inline data rather than time or temperature heuristics, minimizing risk of over- or under-drying.
• Integration capability: Moisture data exported to the dryer’s PLC or SAPAT for closed-loop control, reducing manual intervention and process variability.
• Model performance: Calibration delivered accurate moisture predictions within the specified range when validated against offline Karl Fischer titration results.

Benefits and Practical Applications

• Reagent-free, nondestructive analysis reduces waste and lab overhead.
• Real-time feedback shortens decision loops, accelerating batch throughput.
• Enhanced product consistency by preventing caking, stickiness, and particle damage.
• Alignment with PAT initiatives and pharmacopoeia guidelines (Ph. Eur. 2.2.40, USP <1119>) for continuous process validation.

Future Trends and Opportunities

The integration of inline NIRS with smart plant architectures and Industry 4.0 platforms will drive fully automated granulation processes. Advances in multivariate analysis and machine learning will refine model robustness, enabling predictive control and digital twins. Expansion to other critical process parameters—such as binder spray rate or API distribution—can further enhance quality-by-design approaches.

Conclusion

Inline NIR moisture analysis in pilot-scale granulation demonstrates clear advantages in process understanding, quality assurance, and operational efficiency. The combination of rapid, noninvasive measurement and seamless integration into control systems supports robust process control and regulatory compliance.

References

• AN-NIR-016 Near-infrared spectroscopy for monitoring a single-pot granulator
• AB-358 Analysis of residual moisture in a lyophilized pharmaceutical product by NIRS
• AN-PAN-1050 Inline moisture analysis in fluid bed dryers by NIRS
• TA-048 Near-infrared spectroscopy for pharmaceutical analysis