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Direct measurement of molecular mobility and crystallisation of amorphous pharmaceuticals using terahertz spectroscopy.

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Sibik, Juraj 
Zeitler, J Axel 


Despite much effort in the area, no comprehensive understanding of the formation and behaviour of amorphous solids has yet been achieved. This severely limits the industrial application of such materials, including drug delivery where, in principle, amorphous solids have demonstrated their great usefulness in increasing the bioavailability of poorly aqueous soluble active pharmaceutical ingredients. Terahertz time-domain spectroscopy is a relatively novel analytical technique that can be used to measure the fast molecular dynamics of molecules with high accuracy in a non-contact and non-destructive fashion. Over the past decade a number of applications for the characterisation of amorphous drug molecules and formulations have been developed and it has been demonstrated how this technique can be used to determine the onset and strength in molecular mobility that underpins the crystallisation of amorphous drugs. In this review we provide an overview of the history, fundamentals and future perspective of pharmaceutical applications related to the terahertz dynamics of amorphous systems.



Amorphous stability, Caged dynamics, Dielectric relaxation, Far-infrared, Glass transition, Johari–Goldstein β relaxation, Molecular mobility, Terahertz spectroscopy, Chemistry, Pharmaceutical, Crystallization, Molecular Dynamics Simulation, Pharmaceutical Preparations, Terahertz Spectroscopy

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Adv Drug Deliv Rev

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Elsevier BV
Engineering and Physical Sciences Research Council (EP/J007803/1)
We would like to acknowledge the U.K. Engineering and Physical Sciences Research Council (EP/J007803/1) as well as MedImmune for funding.