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J Pharm Sci. 2017 Jan;106(1):5-27. doi: 10.1016/j.xphs.2016.05.001. Epub 2016 Jun 30.

Interrelationships Between Structure and the Properties of Amorphous Solids of Pharmaceutical Interest.

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School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin 53706.
Seventh Street Development Group, Kure Beach, North Carolina 28449. Electronic address:


This commentary explores fundamental issues associated with the structure of amorphous solids of pharmaceutical interest in terms of the effects of such structure on: various thermodynamic properties; the glass transition temperature, Tg, physical aging of glasses, polyamorphism; molecular mobility by primary diffusive and secondary Johari-Goldstein relaxations; solid-state crystallization; water vapor absorption; and the formation of active pharmaceutical ingredients-polymer dispersions. Recognizing that small organic molecules, as well as polymers used pharmaceutically, tend to exhibit highly "fragile" behavior in the supercooled liquid state, that is, significant increases in relaxation time or viscosity with decreasing temperature as Tg is approached, particular emphasis has been placed on local and global structural factors, that appear to give rise to the nonexponential dependence of the structural relaxation time and viscosity associated with spatial and temporal heterogeneity, at temperatures below the "crossover temperature," Tx, (1.2-1.4 Tg), using theoretical random close packing and "jamming" models. Utilizing a "2-region" structural model of the glassy state, wherein glasses consist of clustered domains surrounded by a higher energy and less dense "microstructure," it has been possible to better understand the underlying structural factors that give rise to a number of important phenomena which occur in the glassy state.


amorphous; fragility; glass; glass transition; hygroscopicity; mobility; physical stability; solid dispersion; structure; water in solids

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