Dependence of Signal on Depth in Transmission Raman Spectroscopy

Recently, transmission Raman spectroscopy has been shown to be a valuable tool in the volumetric quantification of pharmaceutical formulations. In this work a Monte Carlo simulation and experimental study are performed to elucidate the dependence of the Raman signal on depth from the viewpoint of probing pharmaceutical tablets and powders in this experimental configuration. The transmission Raman signal is shown to exhibit a moderate bias toward the center of the tablets and this can be considerably reduced by using a recently developed Raman signal-enhancing concept, the “photon diode.” The enhancing element not only reduces the bias but also increases the overall Raman signal intensity and consequently improves the signal-to-noise ratio of the measured spectrum. Overall, its implementation with appropriately chosen reflectivity results in a more uniform volumetric sampling across the half of the tablet where the photon diode is used (or across the tablet's entire depth if two photon diodes are used on each side of tablet) and enhanced overall sensitivity. These findings are substantiated experimentally on a segmented tablet by inserting a poly(ethelyne terephthalate) (PET) film doped with TiO₂ at different depths and monitoring its contribution to the overall transmission Raman signal from the segmented tablet. The numerical simulations also indicate considerable sensitivity of the overall Raman signal to the absorption of the sample, which is in line with large migration distances traversed by photons in these measurements. The presence of sample absorption was shown numerically to reduce the signal enhancement effect while the overall depth-dependence profile remained broadly unchanged. The absorption was also shown to produce a depth profile with the photon diode similar to that without it, although with a reduced absolute intensity of Raman signals and diminished enhancement effect.