Polymorphic drugs examined with neutron spectroscopy: Is making more stable forms really that simple?
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Polymorphic drugs examined with neutron spectroscopy: Is making more stable forms really that simple? / Tsapatsaris, Nikolaos; Landsgesell, Sven; Koza, Michael Marek; Frick, Bernhard; Boldyreva, Elena; Nunes Bordallo, Heloisa.
I: Chemical Physics, Bind 427, 124-128, 12.12.2013.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Polymorphic drugs examined with neutron spectroscopy: Is making more stable forms really that simple?
AU - Tsapatsaris, Nikolaos
AU - Landsgesell, Sven
AU - Koza, Michael Marek
AU - Frick, Bernhard
AU - Boldyreva, Elena
AU - Nunes Bordallo, Heloisa
PY - 2013/12/12
Y1 - 2013/12/12
N2 - Understanding polymorphism in pharmaceutical ingredients is a long- standing challenge. 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, 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.
AB - Understanding polymorphism in pharmaceutical ingredients is a long- standing challenge. 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, 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.
U2 - 10.1016/j.chemphys.2013.04.016
DO - 10.1016/j.chemphys.2013.04.016
M3 - Journal article
VL - 427
JO - Chemical Physics
JF - Chemical Physics
SN - 0301-0104
M1 - 124-128
ER -
ID: 45248595