Preparation and characterization of carprofen co-crystals

Carprofen co-crystals with selected co-formers were prepared by solvent evaporation and wet/dry grinding methods. Their effective formation was investigated by thermal analysis, FT-IR, X-ray single crystal and powder diffraction and SEM-EDS. This last technique has been applied for the first time to co-crystals since it provides unambiguous confirmation of co-crystal formation. Among the investigated co-formers we studied, only 4,4'-dipyridyl yields co-crystals. Two different crystal structures are obtained when the molar ratio of carprofen : 4,4'-dipyridyl is 2 : 1 (triclinic cell) and 1 : 1.5 (monoclinic cell). The asymmetric triclinic cell (Z = 2) contains two carprofen and two half 4,4'-dipyridyl moieties while the monoclinic cell (Z = 4) contains a single carprofen, and one and a half 4,4'-dipyridyl moieties. Several hydrogen-bond supramolecular synthons can be identified in the solid state. For both the 2 : 1 and 1 : 1.5 co-crystals, the main hydrogen-bond interaction consists of an O-H center dot center dot center dot N heterosynthon involving, as a donor, the COOH group of carprofen and, as a H-acceptor, the nitrogen of a 4,4'-dipyridyl molecule. The two co-crystals have characteristic FT-IR spectra and slightly different melting temperatures. X-Ray powder diffraction patterns of the 1 : 1 and 1 : 2 compositions reveal a mixture of phases, whose amount is quantified with Rietveld analysis.