Hyperspectral Raman Line Mapping as an Effective Tool To Monitor the Coating Thickness of Pharmaceutical Tablets

Abstract

Protective chemical coatings are deposited on drugs during the manufacturing process for the purpose of controlling the pharmacokinetics of active pharmaceutical ingredients (APIs). Although manufacturers attempt to coat all the tablets uniformly, the film thickness of an individual drug is statistically different and depends on the measuring position of the anisotropic structure, and analytical methods for measuring coating thickness must be robust to statistical and geometrical aberrations. Herein, we demonstrate that a spatially offset Raman-spectroscopy-based line mapping method offered excellent calibration and prediction of the coating thickness of 270 acetaminophen (N-acetyl-para-aminophenol, paracetamol) tablets. Raman-scattered light resurfaced back from the coating and APIs, and offset-resolved spectra were projected according to the vertical positions in an imaging sensor. The Raman intensity ratio between the coating substance and the inner APIs is a key parameter in the analysis, and its variation with respect to the spatial offset is proportional to the coating thickness and duration. The results of this study have implications for the rapid spectroscopic thickness measurement of industrial products coated with transparent or translucent materials.