Identification of a pharmaceutical tablet’s origin using FT Near-IR and Principal Component Analysis

Significance of the Topic

The ability to trace the origin of pharmaceutical tablets is critical for quality control, regulatory compliance, and consumer safety. With patent expirations driving generic competition, rapid and reliable methods are needed to verify bioequivalence and detect counterfeit or mislabeled products.

Objectives and Overview of the Study

This study aimed to demonstrate how Fourier Transform near-infrared (FT-NIR) spectroscopy combined with principal component analysis (PCA) can distinguish cetirizine hydrochloride tablets produced by various manufacturers, including branded Zyrtec and multiple generic sources.

Methodology and Instrumentation

Mid-IR spectra were acquired using attenuated total reflection (ATR) to obtain molecular fingerprints, while FT-NIR data were collected in diffuse reflectance mode via an integrating sphere for rapid, non-destructive analysis. A micro-ATR imaging accessory further provided high-resolution surface maps. Multivariate PCA was applied to second-derivative spectral data to identify natural clustering based on excipient and formulation differences.

Used Instrumentation

• Agilent Cary 660 FTIR spectrometer (Mid-IR and Near-IR capability)
• Pike MIRacle Diamond/ZnSe ATR accessory
• Pike IntegrateIR Near-IR diffuse reflectance integrating sphere
• Agilent 660 FTIR/620 FTIR Imaging system with 64×64 FPA detector

Main Results and Discussion

Mid-IR ATR spectra provided clear functional-group fingerprints but exhibited variability due to surface heterogeneity and contact pressure. FT-NIR spectra, though less information-dense visually, yielded robust chemometric models. PCA of 90 spectra (6 distributors, 5 tablets each, 3 replicates) showed distinct clusters correlating to tablet origin and formulation. Micro-ATR imaging of a branded Zyrtec tablet revealed micro-scale inhomogeneity in API and excipient distribution, explaining spectral variance observed in ATR measurements.

Benefits and Practical Applications

• Non-destructive analysis with minimal sample preparation
• Rapid throughput suitable for high-volume quality control
• Ability to differentiate manufacturers and detect counterfeit products
• Versatility for solids, powders, and packaged goods

Future Trends and Potential Applications

Future developments include expanding PCA databases with multiple batches for improved classification accuracy, integrating hyperspectral imaging with real-time chemometrics, and deploying portable FT-NIR analyzers for in-field authenticity testing. Artificial intelligence and machine learning tools will further enhance pattern recognition and predictive capabilities.

Conclusion

This work highlights FT-NIR spectroscopy paired with PCA as an efficient and reliable approach to trace the origin of pharmaceutical tablets. Complementary ATR-Imaging offers detailed surface chemical maps, supporting deeper quality investigations. Together, these techniques provide powerful tools for the pharmaceutical industry’s QC, regulatory, and anti-counterfeiting efforts.

Reference

1. Smith A. Big Pharma Teaches Old Drugs New Tricks. CNNMoney, 2007.
2. Whitemore E. Development of FDA-Regulated Medical Products. 2004.
3. Pisano DJ, Mantus D. FDA Regulatory Affairs: A Guide for Prescription Drugs, Medical Devices, and Biologics. 2004.
4. Bio-Rad. AnalyzeIt MVP. 2009.
5. Pfizer. Zyrtec® Prescribing Information. 2006.