Structure–property correlations in piracetam polytypes
Open Access
- 23 December 2020
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in CrystEngComm
- Vol. 23 (5), 1226-1233
- https://doi.org/10.1039/d0ce01694b
Abstract
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.Keywords
Funding Information
- Natur og Univers, Det Frie Forskningsråd (DFF-1323-00122)
- Københavns Universitet
This publication has 51 references indexed in Scilit:
- Solubility of the Metastable Polymorph of Piracetam (Form II) in a Range of SolventsJournal of Chemical & Engineering Data, 2012
- In Situ Monitoring of Supersaturation and Polymorphic Form of Piracetam during Batch Cooling CrystallizationOrganic Process Research & Development, 2011
- Electron and Electrostatic Properties of Three Crystal Forms of PiracetamCrystal Growth & Design, 2011
- Efficient computer modeling of organic materials. The atom–atom, Coulomb–London–Pauli (AA-CLP) model for intermolecular electrostatic-polarization, dispersion and repulsion energiesNew Journal of Chemistry, 2011
- Mechanical Anisotropy in Crystalline Saccharin: Nanoindentation StudiesCrystal Growth & Design, 2010
- Solvent Influences on Metastable Polymorph Lifetimes: Real-Time Interconversions Using Energy Dispersive X-Ray Diffractometry**We dedicate this paper to Professor David Grant. Not only a talented scientist, he was a man who gave freely of his time and ideas to support and encourage others, including ourselves.Journal of Pharmaceutical Sciences, 2007
- Measurement of hardness and elastic modulus by instrumented indentation: Advances in understanding and refinements to methodologyJournal of Materials Research, 2004
- Structure of a metastable phase of piracetam from X-ray powder diffraction using the atom–atom potential methodActa crystallographica Section B, Structural science, crystal engineering and materials, 1995
- An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experimentsJournal of Materials Research, 1992
- Structures of the triclinic and monoclinic modifications of (2-oxo-1-pyrrolidinyl)acetamideActa Crystallographica Section B: Structural Science, Crystal Engineering and Materials, 1982