(M1330-08-48) Quantification and Identity Testing of Soft Gel Capsules using Transmission Raman Spectroscopy

Purpose: Transmission Raman Spectroscopy is a widely accepted technique that is used for content uniformity (CU), assay, and drug product identity (ID) testing of pharmaceutical oral solid dose (OSD) products. TRS100 Raman pharmaceutical analysis system enables fast, non-destructive analysis of tablets and capsules, without the need for chemical preparation or skilled analytical chemists, improving the operational efficiency of quality control (QC) laboratories. The TRS100 uses transmission Raman to provide bulk volumetric analysis of OSD pharmaceutical products. The instrument can analyze active pharmaceutical ingredients (API) and excipients in a range of different sample types including tablets, powders, hard and soft gel capsules. This poster discusses how the TRS100 can be used to generate both a qualitative (ID) and quantitative analysis of soft gel capsules.

Methods: The TRS100 Raman system was used for the analysis of the soft gel capsules. The first part of the analysis focused on the quantification of the soft gel capsules for CU and assay analysis. The second part of the study demonstrated how the TRS100 can be used to verify the identity of soft gel capsules with differing dose strengths. A Partial Least Squares calibration model was used for the quantification of the soft gel capsules. For the calibration, a set of calibration samples with 90 to110% Label Claim of API concentration were prepared. Owing to the practical difficulties of generating an intact calibration set of soft gel capsules, an alternative method was devised. Empty capsule shells were flattened and placed in the TRS100 sample tray. The calibration standard liquid gel was then dispensed on top of the capsule shells. Clear adhesive film was used to seal the base of the tray resulting in the final set of calibration standards. This experimental design provided an excellent approximation of a real capsule, as demonstrated in the results section of the note. The seven calibration standards were analyzed using the TRS100 with a laser power setting of 0.65 W for 10 seconds per sample (exposure 2 seconds x 5 accumulations).The data was preprocessed via first derivative and normalized. When compared to the pure API and Excipient A derivatized spectra, spectral variation was observed in correspondence with concentration of API and the Excipient. Gel capsules with three different dose strengths were analyzed using the TRS100 under the same acquisition settings used for calibration. These samples were used to investigate whether an identification model could be obtained using the TRS100.

Results: The calibration samples were used to build a PLS predictive model in the Solo chemometric software. The chosen model used two latent variables over the spectral range 650 to 1700 cm-1 using 1st derivative, normalized and mean center preprocessing. Excellent model values were obtained, as shown by the linearity (R2 of 0.995) of the calibration. Also, low and similar values for RMSEC and RMSECV of 0.36 and 0.45%, respectively, indicate good accuracy. For this proof-of-concept study, the model was evaluated by testing whole intact finished dose forms. Results indicate excellent prediction accuracy for the API concentration in the soft gel capsules. The predicted concentration of API compared well with the expected 100% LC with an average result of 100.2%LC and a standard deviation of 0.2% and RMSEP of 0.27%. Gel capsules with three different dose strengths were analyzed using the TRS100. A PLS-DA classification model was built. The results indicate clear separation between gel capsules of different dose strengths, allowing them to be easily identified. Distinct clustering of the samples by dose strength demonstrates the suitability of the TRS100 for identification testing of soft gel capsules. Implementation in pharmaceutical QC labs

Conclusion: Transmission Raman spectroscopy (TRS) can provide analysis of a range of pharmaceutical oral solid dose forms, including soft gel capsules. The study has shown that the Agilent TRS100 Raman quantitative pharmaceutical analysis system is suitable for content uniformity, assay, and identity testing of soft gel capsules. The method was fast, requiring only 10 seconds of measurement time, and no sample preparation, solvents, chemicals, or consumables were needed. Given the simplicity and speed of the method, the TRS100 provides an efficient, cost effective, and sustainable workflow for QC testing of soft gel capsules.

References: FDA. Guidance for industry PAT—a framework for innovative pharmaceutical development, manufacturing, and quality assurance. 2004
European medicines Agency (EMA) Guideline on real time release testing (formerly Guideline on parametric release). 2012.
Andrews, D., et. al.; Analytical Method Development Using Transmission Raman Spectroscopy for Pharmaceutical Assays and Compliance with Regulatory Guidelines—Part I: Transmission Raman Spectroscopy and Method Development. Journal of Pharmaceutical Innovation, 13, 121–132, 2018.
Villaumié, J., et. al.; Analytical Method Development Using Transmission Raman Spectroscopy for Pharmaceutical Assays and Compliance with Regulatory Guidelines—Part II: Practical Implementation Considerations. Journal of Pharmaceutical Innovation, 1–14, 2018.

Acknowledgments: This work is also published in an Agilent application note.
https://www.agilent.com/cs/library/applications/application-soft-gel-trs-5994-4096en-agilent.pdf

Soft gel capsules which were analyzed via transmission Raman



Soft gel capsule transmission Raman spectra



soft gel capsule calibration