Pseudo-3D Subsurface Imaging of Pharmaceutical Solid Dosage Forms Using Micro-spatially Offset Low-Frequency Raman Spectroscopy.

A new combinatory Raman subtechnique of low-frequency and micro-spatially offset Raman spectroscopy (denoted micro-SOLFRS) is demonstrated via analysis of pharmaceutical solid dosage forms. A variety of different (multilayer/multicomponent) model systems comprising celecoxib, α-lactose (the anhydrous and monohydrate form), and polyvinylpyrrolidone (PVP) were probed to test the potency of this newly developed technique to, for example, provide qualitative and quantitative information on surface and subsurface layer characteristics, including their thicknesses as well as enable monitoring of surface-driven solid-state form transformations. A simultaneous collection of low- and, the more commonly used, mid-frequency data enabled a direct comparison between these spectral regions, where the low-frequency domain (hence, micro-SOLFRS) proved superior for every respective analysis carried out herein.