Supramolecular architectures of meloxicam carboxylic acid cocrystals, a crystal engineering case study

Meloxicam is a nonsteroidal anti-inflammatory drug with low aqueous solubility and high permeability prescribed for indications of arthritis, primary dysmenorrhea, fever, and pain. In this contribution, we apply crystal engineering and the supramolecular synthon approach to prepare novel meloxicam cocrystal forms with various pharmaceutically acceptable or toxicologically qualified carboxylic acids. As a result, 19 pharmaceutical cocrystals including one cocrystal of a salt are synthesized by solid-state and solution methods. All resulting cocrystals are characterized by X-ray diffraction, infrared, and thermal analyses. In particular, crystal structures of six meloxicam cocrystals are determined and reported, namely, meloxicam•1-hydroxy-2-naphthoic acid cocrystal (1), meloxicam•glutaric acid cocrystal (2), meloxicam•l- malic acid cocrystal of a salt (3), meloxicam•salicylic acid cocrystal form III (4), meloxicam•fumaric acid cocrystal (5), and meloxicam•succinic acid cocrystal (6). The supramolecular assembly of each cocrystal is analyzed and discussed. It is observed that the meloxicam dimer is robust since this motif is observed in five out of six meloxicam cocrystal structures that have been determined. As part of the continuous development, the resulting meloxicam cocrystal forms will be further investigated to explore improved physicochemical and pharmacological properties.