Near-infrared (NIR) assay and content uniformity of tablets

Significance of the Topic

Near-infrared (NIR) spectroscopy offers a rapid, non-destructive approach to assess tablet content uniformity, aligning with regulatory initiatives such as USP content uniformity requirements and FDA Process Analytical Technology (PAT) guidelines. By delivering near-real-time feedback, NIR can enhance process understanding and control compared to traditional HPLC methods.

Study Aims and Overview

This study evaluated a transmission NIR assay using the NIRS XDS MasterLab to determine the content uniformity of chlorpheniramine maleate (CPM) tablets. The objective was to demonstrate a fast, accurate at-line method capable of analyzing multiple tablets within minutes, thereby reducing laboratory workload and supporting timely batch release.

Methodology and Instrumentation

• Sample Composition: Five tablet batches (0 to 2.0 mg CPM per 100 mg tablet; 0.25″ diameter) including placebo and varying API levels.
• Instrument: NIRS XDS MasterLab configured for transmission mode with automated tablet tray for 10-tablet scans per run.
• Spectral Acquisition: Wavelength range 800–1650 nm, 0.5 nm intervals, 32 co-added scans; reference spectrum collected before each set of five tablets.
• Data Pre-treatment: Second derivative transformation, smoothing (segment = 10, gap = 0), and thickness correction to mitigate sample density and pathlength variations.
• Calibration Modeling: Partial least squares (PLS) regression with factor selection based on minimum predicted residual error sum of squares (PRESS), culminating in a six-factor model for robustness.

Main Results and Discussion

Second derivative spectra revealed a prominent absorption band at 1138 nm associated with CPM. The optimized PLS model achieved R² = 0.9998, standard error of calibration (SEC) = 0.0119, standard error of cross-validation (SECV) = 0.0148, and standard error of prediction (SEP) = 0.01. Repeatability assessment on 0.1 mg CPM tablets yielded a precision of 0.0039 and bias of 0.0018. Statistical process control (SPC) charts demonstrated stable performance within ±15% control limits, enabling immediate detection of uniformity issues.

Benefits and Practical Applications

• Time Efficiency: Analysis of ten tablets in under five minutes versus hours required for HPLC.
• Real-Time Monitoring: At-line integration supports immediate process adjustments on the tablet press.
• Resource Savings: Eliminates solvent use and reduces laboratory burden associated with traditional assays.

Future Trends and Opportunities

Further enhancements may include designing calibration sets with finer concentration increments around target label claims to improve model precision. Incorporating inline NIR measurements during pilot and production batches can streamline PAT implementation. Extending this approach to other active pharmaceutical ingredients and dosage forms offers broad applicability across pharmaceutical manufacturing.

Conclusion

This application note demonstrates that transmission NIR spectroscopy on the NIRS XDS MasterLab provides a rapid, accurate, and PAT-compliant method for tablet content uniformity testing. Adoption of this technique can significantly reduce analysis times, minimize reliance on HPLC, and support real-time process control.