Portable Transmission Raman Spectroscopy for At-Line Content Uniformity Testing of Pharmaceutical Tablets

Significance of Topic

Ensuring each tablet contains the correct active pharmaceutical ingredient (API) dosage is essential for patient safety and regulatory compliance. Traditional HPLC-based content uniformity testing is destructive, time-consuming, solvent-intensive, and requires skilled personnel, prompting the need for rapid, noninvasive at-line techniques.

Study Objectives and Overview

This case study evaluates portable transmission Raman spectroscopy for at-line content uniformity testing of tablets formulated with acetaminophen, lactose, and excipients. It demonstrates method creation, validation, and prediction using B&W Tek’s QTRam instrument and integrated chemometric software.

Methodology and Instrumentation

• Sample Preparation: Five binary blends (acetaminophen 10–18% w/w, lactose 10.79–28.66% w/w) plus mannitol, microcrystalline cellulose, and magnesium stearate compressed into ~6 mm diameter, 4.5 mm thick tablets (~140 mg) using a Gamlen press at 392 kg force.
• Instrumentation: QTRam portable Raman spectrometer with 785 nm laser (>340 mW, ~4 mm spot) and QT-Sampler accessory; BWAnalyst software (21 CFR Part 11 compliant) for acquisition; BWIQ for chemometric model building.
• Data Collection: Transmission Raman spectra acquired on both tablet faces, 100% laser power, 20 s integration, three replicates per face.
• Chemometric Modeling: Preprocessing included air-PLS background removal, multiplicative scatter correction, and Savitzky-Golay first derivative. Partial least squares regression modeled acetaminophen (1190–1300, 1530–1700 cm⁻¹) and lactose (285–500, 840–890 cm⁻¹).

Main Results and Discussion

The PLS models yielded strong linearity (acetaminophen R²=0.9929; lactose R²=0.9915) and low RMSE (0.23% and 0.53% w/w). Validation on independent samples produced prediction errors within ±0.17% to ±0.40% w/w. Pass/fail criteria (10–14% for API, 18–30% for lactose) correctly identified out-of-spec tablets during prediction.

Benefits and Practical Applications

• Rapid, nondestructive testing without solvents or consumables.
• At-line deployment streamlines manufacturing and reduces delays.
• Full-volume probing overcomes surface-limited back-scatter methods.
• Integrated software facilitates method setup, validation, and operator-level prediction.

Future Trends and Opportunities

Integration with continuous manufacturing, expansion to multi-component formulations, real-time monitoring, instrument miniaturization, and advanced chemometric algorithms are expected to broaden applications and improve specificity and speed.

Conclusion

Portable transmission Raman spectroscopy with the QTRam system offers a fast, accurate, and noninvasive alternative to HPLC for tablet content uniformity testing. Combined with robust chemometric models and compliant software, it supports efficient at-line quality control in pharmaceutical production.

References

No explicit literature references provided.