Relating the tableting behavior of piroxicam polytypes to their crystal structures using energy-vector models

Piroxicam crystallises into two polytypes, α₁ and α₂ with crystal structures that contain identical molecular layers but differ in the way that these layers are stacked. In spite of having close structural similarity, the polytypes have significantly different powder tabletting behaviour: α₂ forms only weak tablets at low pressures accompanied by extensive capping and lamination, which make it impossible to form intact tablets above 100 MPa, while α₁ exhibits superior tabletability over the investigated pressure range (up to 140 MPa). The potential structural origin of the different behaviour is sought using energy-vector models, produced from pairwise intermolecular interaction energies calculated using the PIXEL method. The analysis reveals that the most stabilising intermolecular interactions define columns in both crystal structures. In α₂, a strongly stabilising interaction between inversion-related molecules links these columns into a 2-D network, while no comparable interaction exists in α₁. The higher dimensionality of the energy-vector model in α₂ may be one contributor to its inferior tabletability. A consideration of probable slip planes in the structures identifies regions where the benzothiazine groups of the molecules meet. The energy-vector models in this region are geometrically similar for both structures, but the interactions are more stabilising in α₂ compared to α₁. This feature may also contribute to the inferior tabletability of α₂.