1 Condensed Matter Physics, The Niels Bohr Institute, Faculty of Science, Københavns Universitet2 ESS3 unknown4 Xray and Neutron Science, The Niels Bohr Institute, Faculty of Science, Københavns Universitet5 Xray and Neutron Science, The Niels Bohr Institute, Faculty of Science, Københavns Universitet
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.