Raman spectroscopy of topiramate under high pressure conditions

Topiramate is a white crystalline solid with powerful anticonvulsant activity and is used to treat epilepsy. Drug manufacturing involves various physical and chemical processes, which may lead to the formation of an unexpected, or undesired, crystalline phase, in a phenomenon known as polymorphism. In this paper, the behavior of topiramate crystal is studied under pressures up to 10.8 GPa using Raman spectroscopy. Under the conditions employed, Raman spectra from topiramate under pressure showed no strong evidence of a phase change, although amorphization may be considered. This may be accounted for by its crystal structure, comprising oppositely running chains of topiramate molecules linked by asymmetric hydrogen bonds, which pose a kinetic barrier against a structural change. It is not yet safe to rule out the existence of topiramate polymorphs, which could possibly be obtained under special crystallization conditions, but not after compression, at least up to 10 GPa. Copyright © 2009 John Wiley & Sons, Ltd. Raman spectra of topiramate were recorded under pressures up to 10.8 GPa, in search of a possible polymorph. Structural changes are observed, suggesting possible amorphization. Vibrational mode wavenumber displacements are discussed, the largest displacements being related to CH stretching.