Predicting Crystallisation of Amorphous Drugs With Terahertz Spectroscopy
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Sibik, J., Lobmann, K., Rades, T., & Zeitler, A. (2015). Predicting Crystallisation of Amorphous Drugs With Terahertz Spectroscopy. Molecular Pharmaceutics, 12 3062-3068. https://doi.org/10.1021/acs.molpharmaceut.5b00330
There is a controversy about the extent to which the primary and secondary dielec- tric relaxations in uence the crystallisation of amorphous organic compounds below the glass transition temperature. Recent studies also point to the importance of fast molecular dynamics on picosecond-to-nanosecond time scales with respect to the glass stability. In the present study we provide terahertz spectroscopy evidence on the crystallisation of amorphous naproxen well below its glass transition temperature and con rm the direct role of Johari-Goldstein (JG) secondary relaxation as a facilitator of the crystallisation. We determine the onset temperature T above which the JG re- laxation contributes to the fast molecular dynamics and analytically quantify the level of this contribution. We then show there is a strong correlation between the increase in the fast molecular dynamics and onset of crystallisation in several chosen amor- phous drugs. We believe that this technique has immediate applications to quantify the stability of amorphous drug materials.
terahertz spectroscopy, amorphous, glass, stability, crystallisation
JS and JAZ would like to acknowledge the UK Engineering and Physical Sciences Research Council for funding (EP/J007803/1).
External DOI: https://doi.org/10.1021/acs.molpharmaceut.5b00330
This record's URL: https://www.repository.cam.ac.uk/handle/1810/248722
Licence URL: http://creativecommons.org/licenses/by/4.0/Attribution 4.0