Agilent TRS100 Raman

Significance of the topic

Transmission Raman spectroscopy (TRS) addresses a critical need in pharmaceutical quality control by enabling rapid, non-destructive analysis of intact tablets, capsules, and other dosage forms. By quantifying active pharmaceutical ingredients (APIs), polymorphs, and excipients in seconds without sample preparation or consumables, TRS improves throughput, reduces operating costs, and supports real-time release testing in manufacturing environments.

Study Objectives and Overview

The article presents the Agilent TRS100 Raman system, designed for streamlined QC workflows. Key goals include demonstrating fast content uniformity (CU), assay, and identification (ID) testing; comparing TRS to conventional wet-chemistry and near-infrared methods; and illustrating the system’s compliance with regulatory standards for pharmaceutical analysis.

Methodology and Used Instrumentation

The Agilent TRS100 employs transmission Raman spectroscopy with an 830 nm Class 1 laser to generate feature-rich spectra through intact dosage units. Quantitative models are built using a lean calibration design of experiments (DoE) in accordance with ICH Q2(R1), Q8–Q10 guidelines. Key instrument features include integrated sample trays for up to 300 units, automatic calibration with NIST/ASTM standards, Agilent ContentQC software, and an embedded Eigenvector Solo chemometrics engine. Optional beam enhancer technology further increases sensitivity and speed.

Main Results and Discussion

• Throughput: TRS100 analyzes hundreds of intact tablets or capsules in minutes, reducing total QC cycle time for an eight-batch campaign to approximately 120 minutes versus 1,700 minutes using HPLC.
• Sensitivity: Limits of detection and quantification for APIs and polymorphs reach 0.1 – 1 % w/w, comparable to ssNMR but with analysis times of about 10 seconds per sample.
• Robustness: TRS shows low sensitivity to moisture, particle size, coating thickness, and tablet density, enabling reliable bulk-averaged measurements, including polymorph hotspots.

Practical Benefits and Applications

• Eliminates solvents, consumables, and extensive sample preparation, lowering per-batch cost and resource demands.
• Supports large-n CU testing (>100 units) for in-process control (IPC), process validation, and real-time release testing (RtRT).
• Enables simultaneous multi-API quantification in a single scan, streamlining formulation development and stability studies.

Future trends and applications

Transmission Raman is poised to integrate with advanced process analytical technology (PAT) frameworks and continuous manufacturing lines. Emerging prospects include automated feedback loops for process control, expanded use in low-dose and complex combination products, and integration with machine learning for accelerated method development.

Conclusion

The Agilent TRS100 Raman system delivers a rapid, cost-effective, and regulatory-compliant solution for pharmaceutical QC, outperforming traditional wet-chemistry and NIR methods. Its high throughput, sensitivity to low-dose APIs and polymorphs, and ease of implementation make it a valuable tool for modern pharmaceutical manufacturing and quality assurance.

References

• Kumar R. et al. Quantitative Polymorph Analysis by Transmission Raman Spectroscopy. American Pharmaceutical Review, 19(1), February 2016.