High-Pressure Studies of Pharmaceuticals:  An Exploration of the Behavior of Piracetam

DOI: 10.1021/cg0607710

Authors: Francesca P. A. Fabbiani (School of Chemistry and Centre for Science at Extreme Conditions, The University of Edinburgh, U.K.) , Dave Allan (Diamond Light Source) , William I. F. David (Rutherford Appleton Laboratory, Didcot, U.K.) , Alistair J. Davidson (School of Chemistry and Centre for Science at Extreme Conditions, The University of Edinburgh, U.K.) , Alistair Lennie (Diamond Light Source) , Simon Parsons (School of Chemistry and Centre for Science at Extreme Conditions, The University of Edinburgh, U.K.) , Colin Pulham (University of Edinburgh) , John Warren (University of Liverpool)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Crystal Growth & Design , VOL 7 (6) , PAGES 1115 - 1124

State: Published (Approved)
Published: May 2007

Abstract: The structural response of the nootropic drug piracetam (2-oxo-pyrrolidineacetamide) to both direct compression and high-pressure recrystallization from aqueous solution is reported. Crystals obtained by these methods have been characterized in situ by single-crystal X-ray diffraction. Compression of form II between pressures of 0.45-0.70 GPa caused a reversible, single- crystal to single-crystal transition to give a new polymorph, form V. Crystallization from a dilute aqueous solution of piracetam at a pressure of 0.6 GPa via crystallization of high-pressure ice-VI resulted in the formation of a previously unreported dihydrate. The molecular packing arrangements of these new structures are compared with the known polymorphs and hydrates of piracetam. This study highlights how the systematic variation of pressure is a powerful method for the exploration of polymorphism and solvate formation and has the potential to add a further dimension to polymorph screening of pharmaceuticals.

Subject Areas: Chemistry, Medicine

Facility: SRS Daresbury