Probing Pharmaceutical Mixtures during Milling: The Potency of Low-Frequency Raman Spectroscopy in Identifying Disorder.
Mol Pharm
; 14(12): 4675-4684, 2017 12 04.
Article
em En
| MEDLINE
| ID: mdl-29091447
ABSTRACT
This study uses a multimodal analytical approach to evaluate the rates of (co)amorphization of milled drug and excipient and the effectiveness of different analytical methods in detecting these changes. Indomethacin and tryptophan were the model substances, and the analytical methods included low-frequency Raman spectroscopy (785 nm excitation and capable of measuring both low- (10 to 250 cm-1) and midfrequency (450 to 1800 cm-1) regimes, and a 830 nm system (5 to 250 cm-1)), conventional (200-3000 cm-1) Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR), and X-ray powder diffraction (XRPD). The kinetics of amorphization were found to be faster for the mixture, and indeed, for indomethacin, only partial amorphization occurred (after 360 min of milling). Each technique was capable of identifying the transformations, but some, such as low-frequency Raman spectroscopy and XRPD, provided less ambiguous signatures than the midvibrational frequency techniques (conventional Raman and FTIR). The low-frequency Raman spectra showed intense phonon mode bands for the crystalline and cocrystalline samples that could be used as a sensitive probe of order. Multivariate analysis has been used to further interpret the spectral changes. Overall, this study demonstrates the potential of low-frequency Raman spectroscopy, which has several practical advantages over XRPD, for probing (dis-)order during pharmaceutical processing, showcasing its potential for future development, and implementation as an in-line process monitoring method.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Análise Espectral Raman
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Química Farmacêutica
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Composição de Medicamentos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Mol Pharm
Assunto da revista:
BIOLOGIA MOLECULAR
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FARMACIA
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FARMACOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Nova Zelândia