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

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.

Development of Inline Near-Infrared Spectroscopy Method for Real-Time Monitoring of Blend Uniformity of Direct Compression and Granulation-Based Products at Commercial Scales.

Blending is a critical intermediate unit operation for all solid oral formulations. For blend uniformity testing, API content in the blend must be quantified precisely. A detailed study was conducted to demonstrate the suitability of inline NIR (near-infrared) spectroscopy for blend uniformity testing of two solid oral formulations: existing direct compression (DC) product with a multistep blending process and granulation-based product with API granules. Both qualitative and quantitative methods were developed at a laboratory scale using statistical moving block standard deviation (MBSD) and multivariate data analysis such as principal component analysis (PCA) and partial least squares (PLS) regression. The qualitative MBSD method demonstrated that there was no need for multiple steps for the existing DC product. Hence, a simplified single-step process was developed for blending. Quantitative PLS models for blending processes of both the products were developed, validated, and successfully implemented at a commercial scale for the real-time release of blends. Results obtained from the validated model were in good agreement with the current method of sampling and chromatography.

Nitrogen Fixation by Gliding Arc Plasma: Better Insight by Chemical Kinetics Modelling.

The conversion of atmospheric nitrogen into valuable compounds, that is, so-called nitrogen fixation, is gaining increased interest, owing to the essential role in the nitrogen cycle of the biosphere. Plasma technology, and more specifically gliding arc plasma, has great potential in this area, but little is known about the underlying mechanisms. Therefore, we developed a detailed chemical kinetics model for a pulsed-power gliding-arc reactor operating at atmospheric pressure for nitrogen oxide synthesis. Experiments are performed to validate the model and reasonable agreement is reached between the calculated and measured NO and NO2 yields and the corresponding energy efficiency for NOx formation for different N2 /O2 ratios, indicating that the model can provide a realistic picture of the plasma chemistry. Therefore, we can use the model to investigate the reaction pathways for the formation and loss of NOx . The results indicate that vibrational excitation of N2 in the gliding arc contributes significantly to activating the N2 molecules, and leads to an energy efficient way of NOx production, compared to the thermal process. Based on the underlying chemistry, the model allows us to propose solutions on how to further improve the NOx formation by gliding arc technology. Although the energy efficiency of the gliding-arc-based nitrogen fixation process at the present stage is not comparable to the world-scale Haber-Bosch process, we believe our study helps us to come up with more realistic scenarios of entering a cutting-edge innovation in new business cases for the decentralised production of fertilisers for agriculture, in which low-temperature plasma technology might play an important role.