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Predicting Crystallization of Amorphous Drugs with Terahertz Spectroscopy.


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Authors

Sibik, Juraj 
Löbmann, Korbinian 
Rades, Thomas 
Zeitler, J Axel 

Abstract

There is a controversy about the extent to which the primary and secondary dielectric relaxations influence the crystallization 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 crystallization of amorphous naproxen well below its glass transition temperature and confirm the direct role of Johari-Goldstein (JG) secondary relaxation as a facilitator of the crystallization. We determine the onset temperature Tβ above which the JG relaxation 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 crystallization in several chosen amorphous drugs. We believe that this technique has immediate applications to quantify the stability of amorphous drug materials.

Description

Keywords

amorphous, crystallization, glass, stability, terahertz spectroscopy, Acetaminophen, Calorimetry, Differential Scanning, Crystallization, Drug Stability, Flufenamic Acid, Indomethacin, Kinetics, Molecular Dynamics Simulation, Naproxen, Simvastatin, Temperature, Terahertz Spectroscopy, X-Ray Diffraction

Journal Title

Mol Pharm

Conference Name

Journal ISSN

1543-8384
1543-8392

Volume Title

12

Publisher

American Chemical Society (ACS)
Sponsorship
Engineering and Physical Sciences Research Council (EP/J007803/1)
JS and JAZ would like to acknowledge the UK Engineering and Physical Sciences Research Council for funding (EP/J007803/1).