Lornoxicam Salts: Crystal Structures, Conformations, and Solubility

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.