Raman microimaging as an analytical technique for simultaneous quantification and localization of active principles in pharmaceutical solid dosage forms

Raman microimaging, as a product of Raman microspectroscopy mapping and multivariate analysis, was used for the localization and quantification of active pharmaceutical ingredients (APIs) in tablets made in laboratory. This was done to develop an analytical strategy to simultaneously recover qualitative and quantitative information of solid dosage forms at a microscopic level by using a nondestructive method. A chemical system, composed of acetaminophen (AMP), caffeine, and one excipient (microcrystalline cellulose), was subjected to chemometric analysis through principal component analysis (PCA) and multivariate curve resolution with alternating least squares (MCR–ALS). This was done by using Raman spectra obtained from microscopic images with pixel sizes of 15 × 15 μm to localize the APIs in the tablets. Partial least squares (PLS) was applied as a calibration method to obtain bulk and single‐pixel concentrations of APIs in the samples. MCR–ALS provided better results than PCA for the localization of APIs. PLS achieved satisfactory root mean standard error values in the external validation set (