Abstract
Surface-enhanced, low-frequency Raman spectroscopy (SELFRS) was explored for its potential as a structural screening tool within pharmaceutical applications, including facile small-scale multicomponent analysis. Paracetamol was used as the model drug, and its crystallization behavior with or without the presence of a templating agent (benzoic acid) was investigated using commercial silver-based SERS substrates. The Raman imaging was carried out using two different LFR-enabled instruments employing 532 and 785 nm incident lasers, where each of the setups showed certain affinity for differentiating lattice vibrations of the polymorphic forms of interest: form I and form II. A comparison of SELFRS, SERS, and their combination using chemometrics showed the potential for the LFR spectral range to improve surface-enhanced measurements either individually or in combination with the typically-used fingerprint region without the need to alter the experimental configuration. Additionally, the use of crystallization additives that helped to drive the formation of metastable form II was shown using SELFRS to provide additional mechanistic understanding of the template-assisted crystallization processes.
Original language | English |
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Journal | Analytical Chemistry |
Volume | 96 |
Issue number | 43 |
Pages (from-to) | 17100-17108 |
ISSN | 0003-2700 |
DOIs | |
Publication status | Published - 2024 |
Bibliographical note
Funding Information:The authors acknowledge the Novo Nordisk Foundation for supporting this work. B.J.B. and K.B. are supported by a Novo Nordisk Laureate Research Fellowship awarded to B.J.B.
Publisher Copyright:
© 2024 American Chemical Society.