(493m) Robust Monitoring of Pharmaceutical Manufacturing Operations Based On Combined NIR and Raman Spectroscopy

The introduction of modern process monitoring methods into pharmaceutical manufacturing operations is one of the keys in moving away from the traditional endpoint-controlled manufacturing towards flexible, understood and actively controlled processes. Near-infrared (NIR) and Raman spectroscopy are both well-suited for online monitoring applications as they provide fast, non-invasive measurements. In addition, the feasibility of process monitoring based on NIR and Raman has already been successfully demonstrated in off-line and laboratory-scale investigations, and hardware solutions for laboratory and workshop applications are commercially available.

In general, NIR and Raman spectra often have similar peaks, but in many cases the information provided by the two spectroscopic methods is not redundant but rather complementary. A combined NIR and Raman process monitoring approach could therefore often provide a deeper level of insight into the investigated manufacturing operations than a single spectroscopic technology could provide.

The aim of this work is thus to assess the possibilities of a combined NIR and Raman process monitoring system in order to investigate if and how process monitoring could be improved by applying a combined NIR and Raman approach instead of using each spectroscopic method alone. In this work, both spectroscopic methods are applied in the analysis of blends of an API and one or two excipients. The spectral information gained by applying the spectrometers is used to determine the chemical identity of the constituents and the composition of the binary and ternary blends. The results of three different cases are compared: (i) data derived from an evaluation of the NIR spectra alone (ii) data derived from an evaluation of the Raman spectra alone and (iii) data derived by a combined evaluation of NIR and Raman spectra. A comparative evaluation of the results provided by NIR, Raman and the combined approach provides an insight into the possibilities and the limitations of the spectroscopic methods for the case of dry pharmaceutical powder blend investigations.