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

Significance of the Topic

Authentication and traceability of pharmaceutical tablets are critical for patient safety, regulatory compliance and protection against counterfeit or substandard products. Identifying the origin of a tablet formulation helps ensure consistent bioequivalence, quality control, and supply chain integrity, especially when generic versions enter the market after patent expiration.

Objectives and Study Overview

This study aimed to differentiate the origin of cetirizine hydrochloride tablets (brand and generic) by combining Fourier-transform Near-infrared (FT-NIR) spectroscopy with Principal Component Analysis (PCA). Mid-IR data were also acquired for spectral fingerprinting and to support imaging experiments.

Methodology

• Six distributors supplied tablet samples; five tablets per distributor were run in triplicate.
• Mid-IR spectra were collected using ATR sampling to obtain functional-group fingerprints.
• Near-IR spectra were acquired via an integrating-sphere diffuse-reflection accessory to allow high-throughput, non-destructive analysis on intact tablets.
• Spectra were preprocessed (second derivative, Pareto scaling) and exported to chemometric software for PCA.
• One sample was further examined by micro-ATR imaging using a focal-plane-array detector to map surface chemistry at ~1 µm resolution.

Instrumentation

• Agilent Cary 660 FTIR spectrometer (Mid-IR and Near-IR sources)
• Beamsplitters: KBr (Mid-IR), quartz (Near-IR)
• Detectors: DLaTGS and InGaAs
• Sampling accessories:

• Pike MIRacle Diamond/ZnSe ATR for Mid-IR
• Pike IntegrateIR Near-IR integrating sphere accessory
• Micro-ATR imaging accessory with 64×64 focal-plane array

Main Results and Discussion

• Mid-IR ATR spectra provided clear fingerprint peaks for functional groups (e.g., C–O, OH, aromatic rings) but required manual sample handling.
• Near-IR diffuse‐reflection spectra, while less visually detailed, contained sufficient information for multivariate discrimination of tablet origin without sample prep.
• PCA of 90 Near-IR spectra (six origins × five tablets × three replicates) yielded distinct clusters corresponding to manufacturer and formulation differences, even among samples from the same API producer.
• Micro-ATR imaging revealed surface heterogeneity at the micron scale, explaining some spectral variance observed in bulk ATR measurements.

Benefits and Practical Applications

• Rapid, non-destructive screening of intact tablets through plastic or glass packaging.
• Minimal sample preparation and high throughput via the integrating sphere accessory.
• Differentiation of brand and generic formulations based on excipient and coating variations.
• Root‐cause analysis support for manufacturing QA/QC and counterfeit detection.

Future Trends and Potential Applications

• Development of larger, more robust PCA and machine-learning models encompassing multiple batches and additional manufacturers.
• Deployment of portable NIR devices for in-field authenticity testing at points of sale or customs checkpoints.
• Integration of spectral imaging with automated defect and impurity mapping in tablet coatings.
• Expansion to other dosage forms (capsules, powders) and real-time online process monitoring.

Conclusion

The combination of FT-NIR spectroscopy with PCA effectively discriminates the origin of cetirizine tablets, offering a rapid, non-destructive alternative to traditional chromatographic methods. Micro-ATR imaging further enhances understanding of surface composition and formulation heterogeneity, supporting comprehensive quality control.

Reference

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