Crystallization and disorder of the polytypic α 1 and α 2 polymorphs of piroxicam

Abstract

The polytypic α 1 and α 2 polymorphs of piroxicam are described and it is shown that they can be crystallized controllably. Polymorphism of the active pharmaceutical ingredient piroxicam, C 15 H 13 N 3 O 4 S, is investigated with an aim to clarify the identity and crystallization conditions of the α 1 and α 2 polymorphs. The structures are polytypic, containing identical 2-dimensional layers, with different symmetry relationships between the layers. The α 1 structure is orthorhombic and non-centrosymmetric (space group type Pca 2 1 ), while the α 2 structure is monoclinic and centrosymmetric (space group type P 2 1 / c ). α 2 can be crystallized by evaporation from ethanol at 25 °C, while α 1 is obtained by crystallization from the same solvent at 4 °C. The polytypic relationship provides a suitable condition for order–disorder phenomena to be observed in single crystals. Intermolecular interaction energies calculated using the PIXEL method suggest that the centrosymmetric interlayer regions in α 2 involving the pyridyl groups are more stabilising than the corresponding non-centrosymmetric interlayer regions in α 1 . This is consistent with observations of inversion twinning in non-centrosymmetric α 1 crystals. The interlayer regions involving the benzothiazine groups have very similar interaction energies in the two structures.