Effect of High Pressure on the Polymorphs of Paracetamol

Effect of hydrostatic pressure on the two (I – monoclinic and II – orthorhombic) polymorphs of paracetamol was studied by X-ray diffraction in the diamond anvil cell at pressures up to 4.5 GPa (for the monoclinic form) and up to 5.5 GPa (for the orthorhombic form). The two groups of phenomena were studied: (i) the anisotropic structural distortion of the same polymorph, (ii) transitions between the polymorphs induced by pressure. The anisotropy of structural distortion of polymorphs I and II was well reproducible from sample to sample, also from powder samples to single crystals. The bulk compressibility of the two forms was shown to be practically the same. However, a noticeable qualitative difference in the anisotropy of structural distortion was observed: with increasing pressure the structure of polymorph II contracted in all the directions showing isotropic compression in the planes of hydrogen-bonded molecular layers, whereas the layers in the structure of the polymorph I expanded in some directions. Maximum compression in both polymorphs I and II was observed in the directions normal to the molecular layers. The transitions between the polymorphs induced by pressure were poorly reproducible and depended strongly on the sample and on the procedure of increasing/decreasing pressure. No phase transitions were induced in the single crystals of the monoclinic polymorph at pressures at least up to 4GPa, although a partial transformation of polymorph I into polymorph II was observed at increased pressure in powder samples. Polymorph II transformed partly into the polymorph I during grinding. The transformation could be hindered if grinding was carried out in CCl₄. This revised version was published online in August 2006 with corrections to the Cover Date.