Crystal structure of a 2:1 piroxicam-gentisic acid co-crystal featuring neutral and zwitterionic piroxicam molecules

Abstract

A new 2:1 co-crystal of piroxicam and gentisic acid [systematic name: 4-hydroxy-1,1-dioxo-N-(pyridin-2-yl)-2H-1λ6,2-benzothiazine-3-carboxamide-2-(4-oxido-1,1-dioxo-2H-1λ6,2-benzothiazine-3-amido)pyridin-1-ium-2,5-dihydroxybenzoic acid, 2C15H13N3O4S C7H6O4] has been synthesized using a microfluidic platform and initially identified using Raman spectroscopy. In the co-crystal, one piroxicam molecule is in its neutral form and an intramolecular O - H⋯O hydrogen bond is observed. The other piroxicam molecule is zwitterionic (proton transfer from the OH group to the pyridine N atom) and two intramolecular N - H⋯O hydrogen bonds occur. The gentisic acid molecule shows whole-molecule disorder over two sets of sites in a 0.809(2):0.191(2) ratio. In the crystal, extensive hydrogen bonding between the components forms layers propagating in the ab plane.