Polymorphism of Piroxicam: New Polymorphs by Melt Crystallization and Crystal Structure Prediction

Two new polymorphs of piroxicam (Forms VI and VII) were discovered by melt crystallization and crystal structure prediction (CSP). High-quality single crystals were grown from melt microdroplets for structural solution by X-ray diffraction. Relative to the previously known polymorphs obtained mainly by solution crystallization, the new polymorphs are thermodynamically less stable, confirming melt crystallization as an important complement to solution crystallization in polymorph discovery. Although early workers reported that piroxicam is thermally unstable and unsuitable for melt crystallization, our use of melt microdroplets circumvented this problem because of the short exposure to a high temperature. Our CSP identified all known polymorphs of piroxicam including the two new forms with an energy ranking in reasonable agreement with the observed order, as well as low-energy structures not observed by experiment.