Lornoxicam salts: Crystal structures, conformations, and solubility

Abstract

Lornoxicam (LXM), a nonsteroidal anti-inflammatory drug (NSAID), is an amphiprotic molecule that exists as a zwitterion in the solid state. The formation of two strong intramolecular N+-H···O and N-H···O- hydrogen bonds in a stable six-member ring geometry, S(6), renders this otherwise flexible molecule in a rigid conformation (conformer A). A salt screen of LXM was undertaken to improve drug solubility and to study different conformations of the molecule by varying the counterion. As an amphoteric molecule, LXM salts are both cationic (ammonia, piperazine) and anionic (hydrochloric acid, methanesulfonic acid). The crystal structures of these salts exhibit an intramolecular H bond with different conformations of LXM in the acid and base salts (conformations B and C). The conformational variability of LXM in acidic and basic salts is explained by steric and hydrogen bonding factors. All the new salts were characterized by spectroscopic, thermal, powder X-ray diffraction techniques and showed enhanced solubility compared to the free drug. © 2014 American Chemical Society.