Comparison of sampling techniques for in-line monitoring using Raman spectroscopy.

Raman spectroscopy is currently of interest as a process monitoring tool for pharmaceutical unit operations. In this study, the performance characteristics of Raman spectrometers with different sampling optics have been investigated in the context of process monitoring, with emphasis being placed on assessing homogeneity in powder blends and following changes in solid-state form during wet granulation. A novel large spot non-contact Raman sampling device was compared with a traditional small spot size non-contact sampling device and an immersion probe. The large spot non-contact optics provided significant advantages over the standard systems both as a result of the enhanced sampling volume and because of the greater robustness of the system to fluctuations in the sampling distance during the wet granulation process.