Application of combined solid-state NMR and DFT calculations for the study of piracetam polymorphism

Łukasz Szeleszczuk; Dariusz Maciej Pisklak; Tomasz Gubica; Klaudia Matjakowska; Sławomir Kaźmierski; Monika Zielińska-Pisklak

doi:10.1016/j.ssnmr.2018.11.002

Application of combined solid-state NMR and DFT calculations for the study of piracetam polymorphism

Solid State Nucl Magn Reson. 2019 Feb:97:17-24. doi: 10.1016/j.ssnmr.2018.11.002. Epub 2018 Nov 22.

Authors

Łukasz Szeleszczuk¹, Dariusz Maciej Pisklak², Tomasz Gubica², Klaudia Matjakowska², Sławomir Kaźmierski³, Monika Zielińska-Pisklak⁴

Affiliations

¹ Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Department of Physical Chemistry, Chair of Physical Pharmacy and Bioanalysis, Banacha 1, 02-093 Warsaw, Poland. Electronic address: lszeleszczuk@wum.edu.pl.
² Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Department of Physical Chemistry, Chair of Physical Pharmacy and Bioanalysis, Banacha 1, 02-093 Warsaw, Poland.
³ Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Department of Physical Chemistry, Chair of Physical Pharmacy and Bioanalysis, Banacha 1, 02-093 Warsaw, Poland; Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland.
⁴ Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Department of Biomaterials Chemistry, Chair of Analytical Chemistry and Biomaterials, Banacha 1, 02-093 Warsaw, Poland.

PMID: 30508738
DOI: 10.1016/j.ssnmr.2018.11.002

Abstract

Piracetam, a popular nootropic drug, widely used in the treatment of age-associated mental decline and disorders of the nervous system such as Alzheimer's disease and dementia exists under normal pressure in three polymorphic forms (P1, P2 and P3) of different stability. In this work the relative stability of piracetam polymorphs depending on the temperature was studied using the ssNMR spectroscopy combined with ab initio DFT calculations. The ssNMR spectroscopy enabled the analysis of polymorphic phase transition in the case of pure active substance as well as polymorphic form identification in the analysis of the commercial solid dosage formulations. Quantum chemical calculations of phonon density of states were performed to obtain the temperature dependence of the enthalpy, entropy and free energy of the piracetam polymorphs in a quasi-harmonic approximation. GIPAW NMR calculations combined with molecular dynamics were performed to support the chemical shift assignment. The obtained results showed that DFT calculations can be used not only to obtain the NMR parameters but also to predict the influence of the temperature on the stability order of the polymorphic forms of molecular crystals.

Keywords: CASTEP; DFT; GIPAW; Phase transition; Phonon DOS; Piracetam; Polymorphism; Solid-state NMR.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Density Functional Theory*
Magnetic Resonance Spectroscopy*
Molecular Conformation
Molecular Dynamics Simulation
Phase Transition
Piracetam / chemistry*
Temperature

Substances

Piracetam