Towards a real-time release of blends and tablets using NIR and Raman spectroscopy at commercial scales

Abstract

Near Infrared and Raman spectroscopy-based Process Analytical Technology tools were used for monitoring blend uniformity (BU) and content uniformity (CU) for solid oral formulations. A quantitative Partial Least Square model was developed to monitor BU as real-time release testing at a commercial scale. The model having the R², and root mean square error of 0.9724 and 2.2047, respectively can predict the target concentration of 100% with a 95% confidence interval of 101.85–102.68% even after one year. The tablets from the same blends were investigated for CU using NIR and Raman techniques both in reflection and transmission mode. Raman reflection technique was found to be the best and the PLS model was developed using tablets compressed at different concentrations, hardness, and speed. The model with R² and RMSE of 0.9766 and 1.9259, respectively was used for the quantification of CU. Both the BU and CU models were validated for accuracy, precision, specificity, linearity, and robustness. The accuracy was proved against the HPLC method with a relative standard deviation of less than 3%. The equivalency for BU by NIR and CU by Raman was evaluated using Schuirmann’s Two One-sided tests and found equivalent to HPLC within a 2% acceptable limit.

Graphical Abstract

Keywords:

• Process analytical technology
• Near Infrared Spectroscopy
• Raman Spectroscopy
• principal component analysis
• partial least square analysis
• blend uniformity
• content uniformity

Acknowledgments

The authors are thankful to the manufacturing team for executing the batches and the analytical team for doing the reference analysis.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

No funds, grants, or other external support was received for conducting this study.