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Insights into pharmaceutical co-crystallization using coherent Raman microscopy
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DOI：10.1016/j.xphs.2024.10.054.png)
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Abstract
En 中文
Formulating active pharmaceutical ingredients (APIs) as co-crystals requires a thorough understanding of cocrystallization behavior under different process conditions. This study employs two forms of coherent Raman microscopy, narrowband coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS) with spectral focusing, to study co-crystallization via liquid-assisted ball milling. Indomethacin and nicotinamide served as the model API and co-former, and the results were compared with established analytical methods. Narrowband CARS, with univariate peak position analysis, was useful to visualize co-crystal formation, but suffered some degree of signal mixing that affected component identification. Hyperspectral SRS imaging, combined with classical least squares multivariate analysis, separated the different components with high confidence and proved to be a robust and rapid tool to qualitatively and quantitatively image cocrystallization. The coherent Raman imaging results explained divergent co-crystallization endpoints obtained with the conventional solid-state analysis methods. CARS and SRS microscopies also revealed the presence of otherwise undetected trace forms. Finally, we also demonstrated the dramatic reversal of partial co-crystal formation during milling, depending on ethanol content. Overall, the study demonstrates the added value coherent Raman microscopy can provide for analysis of co-crystallization processes. (c) 2024 The Authors. Published by Elsevier Inc. on behalf of American Pharmacists Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Keywords:
Raman spectroscopy
Spectroscopy
Co-crystal(s)
Solid-state
Milling
Analytical chemistry
Imaging method(s)
Poorly water-soluble drug(s)
Phase transformation(s)
Materials science
Journal
IF:
3.8
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1.1W
Citations:
2.6W