Quantification of water in lactose with the OMNIS NIRS Analyzer

Significance of the Topic

Moisture levels in lactose, a major pharmaceutical excipient present in 60–70% of solid dosage forms, critically influence tablet strength, powder flow, and processing efficiency. Excess water leads to stickiness and agglomeration, complicating handling and quality control. Regulatory standards specify water content in lactose monohydrate between 4.5% and 5.5%.

Objectives and Study Overview

• Develop a rapid near-infrared spectroscopy (NIRS) method to quantify water in lactose monohydrate.
• Construct and validate a multivariate calibration model correlating NIR spectra to reference water values.
• Demonstrate method performance versus Karl Fischer oven titration for routine quality control.

Methodology and Instrumentation

Lactose monohydrate samples with controlled water content were prepared by spiking with water or oven drying. Reflectance spectra were acquired in the 1000–2250 nm range using an OMNIS NIR Analyzer Solid in 19 mm vials. Single measurements were performed, and spectral data processed with OMNIS Software and Quant Development module. Cross-validation assessed model robustness and precision.

Instrumentation

• OMNIS NIR Analyzer Solid (1000–2250 nm) with flexible vial holder
• Disposable 19 mm reflection glass vials
• OMNIS Stand-Alone software license
• Quant Development module for calibration

Main Results and Discussion

The NIRS calibration achieved an R² of 0.977, SEC of 0.12% and SECV of 0.14%, indicating strong agreement with Karl Fischer reference values. For a control sample (5.10 ± 0.04% water by KF), the NIRS model predicted 5.138% with a relative standard deviation of 0.029%, confirming high accuracy and reproducibility for routine analysis.

Benefits and Practical Applications

• Rapid measurement in seconds compared to lengthy Karl Fischer oven methods
• Non-destructive, reagent-free analysis reducing consumable costs
• Simple implementation for at-line or in-line quality control
• Enhanced throughput and process efficiency in pharmaceutical production

Future Trends and Potential Applications

Integration of NIRS into continuous manufacturing and process analytical technology (PAT) frameworks will enable real-time moisture monitoring. Expansion of spectral libraries, advanced chemometric algorithms, and AI-driven analysis are expected to further improve model accuracy and extend applications to other excipients and formulations.

Conclusion

OMNIS NIRS offers a fast, accurate, and non-destructive alternative for water determination in lactose, meeting regulatory requirements and enhancing laboratory efficiency. Its high correlation with reference methods and ease of use make it a valuable tool for pharmaceutical quality control.

References

1. Hebbink GA, Dickhoff BHJ. Application of Lactose in the Pharmaceutical Industry. In: Paques M, Lindner C, editors. Lactose. Academic Press; 2019. p. 175–229. doi:10.1016/B978-0-12-811720-0.00005-2
2. Lactose Monohydrate. USP–NF Monograph. DOI:10.31003/USPNF_M44190_04_01