Inline moisture analysis in a pilot scale granulation process by NIRS

Significance of the Topic

Securing precise residual moisture content in pharmaceutical granulation ensures product integrity, prevents particle fracture and caking, and supports continuous manufacturing under PAT guidelines.

Objectives and Study Overview

This study evaluates inline near-infrared spectroscopy (NIRS) for monitoring residual moisture during top-spray granulation processes at pilot scale. The goal is to replace time- or temperature-based endpoints with direct moisture measurements to improve process control and product quality.

Methodology

The monitoring setup involved a NIRS Analyzer PRO operating in the 1100–1650 nm spectral range, fitted with a micro interactance reflectance probe featuring a sample “spoon” and purge ports. Inline data acquisition occurred directly inside the fluid bed dryer, with spectra collected at regular intervals. A reference laboratory method was used to develop and validate the calibration model covering moisture levels from 0 to 60% w/w.

Instrumentation Used

• NIRS Analyzer PRO – FiberSystem (A629281120) with high-resolution diode array detection
• Micro interactance reflectance probe with integrated purge on collection tip
• Fiber-optic cable assembly for reflectance measurements in powders and granules

Main Results and Discussion

Real-time moisture trends displayed an asymptotic decline toward a target endpoint, enabling clear identification of the end-of-drying phase. Inline measurements correlated strongly with off-line reference values, demonstrating accuracy and reproducibility. Integration with the fluid bed dryer’s PLC or PAT software facilitates automated endpoint control, reducing manual sampling delays and rework.

Benefits and Practical Applications

• Rapid, reagent-free, and non-destructive moisture analysis
• Enhanced process understanding and decision-making based on actual moisture data
• Reduced cycle times by eliminating laboratory turnaround
• Compliance with pharmacopoeial standards (Ph. Eur. 2.2.40, USP <1119>) and FDA PAT initiatives
• Potential for closed-loop control to improve batch consistency

Future Trends and Applications

Expected developments include advanced chemometric models using machine learning for improved prediction, multi-sensor integration for comprehensive process analytical control, and seamless embedding of inline NIRS in continuous pharmaceutical manufacturing and Industry 4.0 frameworks.

Conclusion

Inline NIRS monitoring in pilot-scale granulation provides precise, fast, and compliant moisture assessment, streamlining drying operations and enhancing product quality. Adoption of this technology supports robust continuous manufacturing and aligns with regulatory PAT guidelines.

References

1. Metrohm AG. AN-PAN-1048: Inline moisture analysis in a pilot-scale granulation process by NIRS.
2. Metrohm AG. AN-PAN-1050: Inline moisture analysis in fluid bed dryers by NIRS.
3. Metrohm AG. AN-NIR-016: Near-infrared spectroscopy for monitoring a single-pot granulator.
4. Metrohm AG. AB-358: Analysis of residual moisture in a lyophilized pharmaceutical product by NIRS.