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

Importance of Topic

Transmission Raman spectroscopy offers a rapid, non‐destructive, and solvent‐free approach for analyzing pharmaceutical dosage forms. Its ability to probe bulk content without sample preparation significantly enhances quality control throughput and sustainability. Soft gel capsules, widely used for delivering lipid‐soluble active ingredients, present unique challenges for traditional destructive assays. Implementing transmission Raman for these dosage forms addresses industry demands for efficient content uniformity, assay, and identity testing.

Aim and Overview of Study

This study evaluated the Agilent TRS100 system’s capability to perform quantitative and qualitative analysis of soft gel capsules. The objectives included developing calibration models for content uniformity and assay of active pharmaceutical ingredients (APIs) and establishing identity testing for different dosage strengths. Method validation and proof‐of‐concept performance in a simulated QC environment were also assessed.

Methods and Instrumentation

A Partial Least Squares (PLS) calibration model was created using seven API concentration levels (90–110% label claim). Calibration standards were prepared by flattening empty soft gel shells, dispensing liquid formulation, and sealing with adhesive film. Spectra were collected with the TRS100 system under 0.65 W laser power for 10 seconds per sample. Data preprocessing included first derivative transformation and Standard Normal Variate normalization. Model building and classification used Solo chemometric software.

Main Results and Discussion

The PLS model achieved strong linearity (R2 0.995) and low prediction errors (RMSEC 0.36%, RMSECV 0.45%). Validation on intact capsules yielded an average recovery of 100.2% label claim with 0.2% standard deviation and RMSEP of 0.27%. PLS‐DA classification clearly separated three dosage strengths, demonstrating reliable identity testing.

Benefits and Practical Applications

• Fast analysis—10 seconds per sample without preparation
• Non‐destructive testing preserving samples for further use
• No solvents or consumables, reducing costs and waste
• Integrated software solution supporting secure data management and LIMS connectivity

Future Trends and Potential Applications

Advances in chemometric algorithms and hardware may further improve sensitivity and expand applicability to other complex dosage forms. Integration with automated sampling systems and digital QC workflows will enhance throughput. Regulatory acceptance of Raman methods is expected to grow, supporting continuous manufacturing and real‐time release testing.

Conclusion

The Agilent TRS100 transmission Raman system provides a robust, efficient, and green solution for content uniformity, assay, and identity testing of soft gel capsules. Its rapid, solvent‐free approach aligns with modern QC demands, paving the way for streamlined pharmaceutical analysis.

Reference

1. 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.
2. Villaumié J., Andrews D., Geentjens K., Igne B. Analytical Method Development Using Transmission Raman Spectroscopy for Pharmaceutical Assays and Compliance with Regulatory Guidelines—Part II: Practical Implementation Considerations. J Pharm Innov. 14, 2019.
3. Solo, Stand Alone Chemometrics Software. Eigenvector Research Inc.; accessed August 24, 2021.