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Unusually stable glasses may benefit drugs, coatings

December 11, 2006

Just spray and chill. That sums up a new approach to making remarkably stable glassy materials from organic (carbon-containing) molecules that could lead to novel coatings and to improvements in drug delivery. The processing advance is reported in this week's issue of Science [1] by scientists from the University of Wisconsin-Madison and the National Institute of Standards and Technology (NIST) Center for Neutron Research (NCNR).

The researchers suggest that their approach might be useful for preparing pharmaceutical compounds in non-crystalline forms that are readily absorbed by the body. Such "amorphous pharmaceuticals" have been the subject of recent research intended to enhance drug delivery and to enable active therapeutic ingredients to reach targets inside the body.

The new technique entails depositing vapors of organic molecules onto a substrate cooled to 50 degrees (Celsius) below the glass transition temperature-the point at which a compound normally begins to solidify en route to becoming glass, a frozen, liquid-like structure with no long-range internal order. Conceived by UW-Madison chemist Mark Ediger and colleagues, the method short-circuits the conventional cooling process to great practical advantage.

The result, the researchers say, is a dramatically altered internal "energy landscape." The glass molecules position themselves more densely in low-energy valleys that dot this landscape. In contrast, the molecules that make up conventional glasses are dispersed more widely and become "frozen" on higher-energy bluffs and mesas.

Conventional glasses are less stable thermodynamically, because the molecules gradually abandon the higher-energy elevations. During processing or over time, a conventional glass is more apt to convert to a low-energy crystalline order, changing the structural nature of the material. This can be a problem for amorphous pharmaceuticals, in particular. If the internal structure changes during storage, for example, properties such as solubility also will change, potentially undermining the effectiveness of the drug.

Studies at the NCNR confirmed that molecules in glasses prepared with the team's vapor-deposition method were very densely packed, yet true glasses-amorphous in arrangement. Neutron probes also were used to study how molecules diffuse during subsequent annealing of the two types of glass samples. After 16 hours of annealing, molecules in the new glass remained fixed in place. The conventional sample, by contrast, began bulk molecular diffusion after less than 30 minutes of annealing.

[1] S.F. Swallen, K.L. Kearns, M.K. Mapes, Y.S. Kim, R. McMahon, M.D. Ediger, T. Wu, L. Yu, and S. Satija. Organic glasses with exceptional thermodynamic and kinetic stability. Science. Dec. 8, 2006.

National Institute of Standards and Technology (NIST)