Polymorphic drugs examined with neutron spectroscopy: Is making more stable forms really that simple?
(2013) In Chemical Physics 427. p.124-128- Abstract
- Understanding polymorphism in pharmaceutical ingredients is a long-standing challenge in formulation science. A well-known example is paracetamol, C8H9NO2. The marketed stable form I crystallizes with corrugated molecular layers. In contrast, form II, which is thermodynamically favorable at high pressures, has relatively planar layers that can slip over each other without difficulty, but is metastable at ambient conditions. By means of inelastic neutron scattering we demonstrated that the lattice modes of form II exhibit a sudden 1 meV energy shift at 300 K under a pressure of ca 0.4 GPa. Moreover, evidence of an increase of the vibrational energy in both polymorphs was found, which was accompanied, in form I, by an unexpectedly weak... (More)
- Understanding polymorphism in pharmaceutical ingredients is a long-standing challenge in formulation science. A well-known example is paracetamol, C8H9NO2. The marketed stable form I crystallizes with corrugated molecular layers. In contrast, form II, which is thermodynamically favorable at high pressures, has relatively planar layers that can slip over each other without difficulty, but is metastable at ambient conditions. By means of inelastic neutron scattering we demonstrated that the lattice modes of form II exhibit a sudden 1 meV energy shift at 300 K under a pressure of ca 0.4 GPa. Moreover, evidence of an increase of the vibrational energy in both polymorphs was found, which was accompanied, in form I, by an unexpectedly weak increase of the tunnel splitting. These results indicate an anisotropy of the potential surface probed by the methyl rotor, and are discussed in relation to the differences of the strength of the hydrogen bond environment for each polymorph. (C) 2013 Elsevier B. V. All rights reserved. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4273033
- author
- Tsapatsaris, Nikolaos LU ; Landsgesell, Sven ; Koza, Michael M. ; Frick, Bernhard ; Boldyreva, Elena V. and Bordallo, Heloisa N.
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Molecular drugs, Polymorphism, Neutron scattering, Pressure, Hydrogen, bonds
- in
- Chemical Physics
- volume
- 427
- pages
- 124 - 128
- publisher
- Elsevier
- external identifiers
-
- wos:000327773900021
- scopus:84890128604
- ISSN
- 0301-0104
- DOI
- 10.1016/j.chemphys.2013.04.016
- language
- English
- LU publication?
- yes
- id
- be15ac68-4c81-4c45-ad75-67cc4ecd3566 (old id 4273033)
- date added to LUP
- 2016-04-01 13:55:14
- date last changed
- 2022-01-27 21:49:22
@article{be15ac68-4c81-4c45-ad75-67cc4ecd3566,
abstract = {{Understanding polymorphism in pharmaceutical ingredients is a long-standing challenge in formulation science. A well-known example is paracetamol, C8H9NO2. The marketed stable form I crystallizes with corrugated molecular layers. In contrast, form II, which is thermodynamically favorable at high pressures, has relatively planar layers that can slip over each other without difficulty, but is metastable at ambient conditions. By means of inelastic neutron scattering we demonstrated that the lattice modes of form II exhibit a sudden 1 meV energy shift at 300 K under a pressure of ca 0.4 GPa. Moreover, evidence of an increase of the vibrational energy in both polymorphs was found, which was accompanied, in form I, by an unexpectedly weak increase of the tunnel splitting. These results indicate an anisotropy of the potential surface probed by the methyl rotor, and are discussed in relation to the differences of the strength of the hydrogen bond environment for each polymorph. (C) 2013 Elsevier B. V. All rights reserved.}},
author = {{Tsapatsaris, Nikolaos and Landsgesell, Sven and Koza, Michael M. and Frick, Bernhard and Boldyreva, Elena V. and Bordallo, Heloisa N.}},
issn = {{0301-0104}},
keywords = {{Molecular drugs; Polymorphism; Neutron scattering; Pressure; Hydrogen; bonds}},
language = {{eng}},
pages = {{124--128}},
publisher = {{Elsevier}},
series = {{Chemical Physics}},
title = {{Polymorphic drugs examined with neutron spectroscopy: Is making more stable forms really that simple?}},
url = {{http://dx.doi.org/10.1016/j.chemphys.2013.04.016}},
doi = {{10.1016/j.chemphys.2013.04.016}},
volume = {{427}},
year = {{2013}},
}