Defining a strategy for chemical imaging of industrial pharmaceutical samples on Raman line-mapping and global illumination instruments

The performance of line-mapping and global illumination Raman systems for two pharmaceutical tablets and a powder blend are assessed in this study. The chemical images were obtained from the placebo, real tablets, and powder blend by using x20, x50, and x100 objectives, as well as via the (pseudo) confocal set-up. The chemical images were produced via univariate wavenumbers and as re-folded principal component (PC) scores (known as score images). In most cases it was easy to image two or three major components of the tablets directly, while the minor components were only imaged via PC scores. The active pharmaceutical ingredients (APIs) were located relatively easily even if present in quite low concentrations (less than 1%) owing to the high Raman scattering coefficients of these materials. The strength of the Raman signal of the API makes it almost ubiquitous in the chemical images of real tablets. Thorough discussion is given on the strategies used to produce chemical images, the prospects of making composite images of all components present in the tablets, and the effects of packing density with relation to the diffusion of the excitation laser light inside the sample. The strengths and weaknesses of the Raman imaging techniques used are emphasized and suggestions are given regarding which instrument is preferable with respect to the goal of the experiment and material under study. For example, mapping technology is preferred for analyzing minor components, while the global illumination approach is recommended for imaging of spatially isolated strong Raman scatterers.