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

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.