Determination of acetaminophen spatial distribution and content in tablets using confocal micro-Raman spectroscopy mapping

This study focused on the development of an effective method to determine the spatial distribution and content of acetaminophen in intact tablets. We scanned tablets by confocal micro-Raman spectroscopy using live video imaging with a microscope to identify the three ingredients of the tablet formulation, acetaminophen, starch, and hydrated magnesium silicate. Tablets with five different acetaminophen concentrations (5.0–37.5%) were scanned at a spectral resolution of 1000 × 1000 μm. Imaging of tablet surface scans generated characteristic Raman spectra, which were used to rapidly and accurately characterize acetaminophen tablets. The spatial distribution of the drug in the tablet was used to assess the homogeneity of the drug formulation. The tablet composition was determined using single-peak spectra of the raw materials of the tablet formulation as references. Characteristic Raman scanning patterns of acetaminophen tablets were used to determine the composition of different formulations. Importantly, we found that acetaminophen was homogeneously distributed in tablets with low drug concentration. Thus, we developed a confocal micro-Raman spectroscopy method to evaluate the spatial distribution and content of each ingredient in intact acetaminophen tablets. Our new method can be used for the validation of the drug preparation process, the verification of the drug dose, and the authentication of the drug.