Quantification and Identity Testing of Soft Gel Capsules using Transmission Raman Spectroscopy

Significance of the Topic

Transmission Raman Spectroscopy (TRS) offers non-destructive, rapid analysis of pharmaceutical oral solid dosage forms. Its ability to perform bulk volumetric measurements without sample preparation addresses throughput, cost, and sustainability demands in quality control environments.

Objectives and Study Overview

This study evaluates the Agilent TRS100 system for quantitative content uniformity and assay testing, as well as qualitative identity testing of soft gel capsules across varying dose strengths. Calibration, model development, and method validation workflows are assessed to demonstrate feasibility for pharmaceutical QC laboratories.

Methodology

• Sample Preparation: Calibration standards prepared by flattening empty soft gel shells, dispensing liquid gel with defined API concentrations (90–110 % label claim), and sealing with clear adhesive film.
• Data Acquisition: TRS100 measurements at 0.65 W laser power for 10 s per sample (5 accumulations of 2 s), covering a 650–1700 cm⁻¹ spectral range.
• Data Processing: First derivative preprocessing, Standard Normal Variate (SNV) normalization, and mean-centering applied prior to chemometric modeling.

Instrumentation

• Agilent TRS100 Raman pharmaceutical analysis system
• ContentQC software for instrument control and secure data management
• Solo (Eigenvector) chemometric software for PLS and PLS-DA modeling

Main Results and Discussion

• Quantitative Analysis: PLS model with two latent variables achieved R² = 0.995, RMSEC = 0.36 %LC, and RMSECV = 0.45 %LC, demonstrating high accuracy.
• Validation: Prediction of intact capsules yielded an average 100.2 %LC API concentration with 0.2 % SD and RMSEP of 0.27 %LC.
• Identity Testing: PLS-DA classification clearly differentiated capsules of three dose strengths, confirming reliable identity verification.

Benefits and Practical Applications

• Non-destructive and solvent-free workflow reduces time and consumables.
• Fast measurement times (10 s per sample) enhance QC throughput.
• Secure software environment supports compliance with regulatory guidelines.

Future Trends and Applications

As TRS technology matures, integration with automated sample handling and expanded spectral libraries for diverse dosage forms is expected. Coupling TRS with advanced chemometric algorithms may further improve robustness, while adoption in continuous manufacturing could enable real-time release testing.

Conclusion

The Agilent TRS100 provides a rapid, accurate, and sustainable approach for content uniformity, assay, and identity testing of soft gel capsules. Its minimal sample preparation, high throughput, and secure data management make it an efficient solution for pharmaceutical QC laboratories.

References

• Andrews D., Geentjens K., Igne B. et al. Analytical Method Development Using Transmission Raman Spectroscopy for Pharmaceutical Assays and Compliance with Regulatory Guidelines—Part I. J. Pharm. Innov., 13 (2018).
• Villaumié J., Andrews D., Geentjens K., Igne B. et al. Analytical Method Development Using Transmission Raman Spectroscopy—Part II: Practical Implementation Considerations. J. Pharm. Innov., 14 (2019).
• Eigenvector Research Inc. Solo Stand-Alone Chemometrics Software. Accessed August 2021.