Structure-property correlations in piracetam polytypes

Polymorphs II and III of piracetam exhibit a polytypic relationship comprising identical layers of molecules with different relative arrangements. Polymorph II has an interlayer structure in which the piracetam molecules adopt face-to-face and edge-to-edge alignments, while polymorph III adopts a herringbone type arrangement in the interlayer region. The structures are analysed using energy-vector models derived from PIXEL pairwise intermolecular interaction energies. Thermal expansion measurements show that the principal expansion axes are approximately aligned with the unit-cell axes in polymorph III, corresponding to directions within the polytypic layers and perpendicular to them. Expansion perpendicular to the layers is almost twice as large as that along any direction within the layers. Polymorph II shows greater volumetric expansion than polymorph III, and its principal expansion axes are aligned parallel and perpendicular to the planes of the piracetam molecules, rather than along the unit-cell axes. Nanoindentation experiments performed on single crystals along the direction perpendicular to the polytypic layers show that the polymorphs have similar hardness (H) values, but polymorph III has a significantly larger elastic modulus (E). Along the direction nearly parallel to the polytypic layers, polymorph II shows a very similar E value to that perpendicular to the layers, but a significantly smaller H value, implying easier slip between the polytypic layers. The tableting behaviour of bulk polymorph II is superior to that of polymorph III, suggesting greater plasticity for polymorph II, which is likely due to a greater degree of slip.