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Advancing pharmaceutical tablet analysis with laser direct infrared (LDIR) imaging
Yeakub Zaker1, Huzeyfe Yilmaz1, Timothy R Lex1
1Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), Office of Pharmaceutical Quality Research (OPQR), Division of Pharmaceutical Quality Research II (DPQR II), 645 S. Newstead Ave., St. Louis, MO 63110, United States.
Abstract:
Laser direct infrared spectroscopy (LDIR) imaging is an emerging vibrational spectroscopic technique that enables rapid surface imaging by using reflectance spectra to capture critical physicochemical properties, such as chemical identity, particle size, shape, and distribution of components, within minutes or even seconds. Despite its advantages, LDIR imaging technology is still in its developmental stages, particularly in understanding method parameters such as the selection of wavenumber for peak and baseline points and the appropriate step size (pixels) for pharmaceutical analysis. In this study, in-house prepared and commercially available tablets were analyzed using LDIR imaging to assess the effects of method development options, particularly the relationship between step size and data acquisition time. Hyperspectral reflectance mode LDIR images were also collected and compared with those obtained from Raman microscopy to validate the accuracy of the LDIR images. The findings emphasize the need for careful wavenumber selection during method development. LDIR images for the evaluated tablets showed good agreement with Raman mapping and hyperspectral mode data sets, although the mean Feret diameter of particles was consistently smaller (14-40 % for active pharmaceutical ingredients (APIs) in the tested tablets) in the LDIR images. Overall, LDIR demonstrates strong potential as a valuable spectroscopic imaging technology for pharmaceutical applications.
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