Low-frequency Raman spectrophotometer with wide laser illumination on the sample: A tool for pharmaceutical...

This work describes an optical configuration for a Raman spectrophotometer, which permits variation of the laser spot size from 3 to 3000 μm, maintaining a high Raman photons throughput and allowing acquisitions with a short integration time. In addition, the instrument can acquire spectra from the low to middle frequency vibrational range (10 to 2000 cm^-1), on the Stokes and anti-Stokes sides. One of the features of this new optical configuration is the non-use of beam splitters to redirect the scattered light to the detector, which would sacrifice the laser power. The quantitative and qualitative analytical performances of the Raman spectrophotometer were evaluated using chemometric models to predict the concentrations of different active pharmaceutical ingredients (APIs) in mixtures with polymorphs and excipients, as well as by analysis of an API mixture employing hyperspectral imaging. This new optical configuration was shown to be versatile for pharmaceutical purposes and could be used in applications such as the characterization of new drugs or the quality control of raw materials and processes, using normal Raman measurements or SERS (surface-enhanced Raman scattering).