Physical stability of co-amorphous mixtures of highly crystallizable drugs probed by fast dynamics
We propose an elastic neutron scattering investigation to study the correlation between the stability of amorphous state of pure and mixed crystallizable drugs and the fast mobility, i.e. the mean square atomic displacement (MSD) originated by the cage dynamics around the glass transition. Recent molecular dynamics simulations indicate a strong correlation between the amplitude of the picosecond rattling motion inside the cage and the much slower structural relaxation, whose dynamics affect the crystallization kinetics. The elastic intensity of two different drugs, indomethacin and naproxen, respectively good and bad glass-forming, and their mixtures at three different relative weight ratios prepared as co-crystals and amorphized via melt-quenching, will be investigated under temperature scans from very low temperature up to some degrees above Tg. The proposed samples show different fragility and stability versus recrystallization from the amorphous state. The suggested experiment could prove that fast cage vibrational amplitude can be a useful predictor of the stability of the metastable amorphous state.
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Simone Capaccioli; M. Alderighi; valeria libera; NATALI Francesca; SONAGLIONI Daniele and TOMBARI ELPIDIO. (2023). Physical stability of co-amorphous mixtures of highly crystallizable drugs probed by fast dynamics. Institut Laue-Langevin (ILL) doi:10.5291/ILL-DATA.6-05-1074
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