Zwitterionic nature of tenoxicam: crystal structures and thermal analyses of a polymorph of tenoxicam and a 1:1 tenoxicam:acetonitrile solvate

• Published in: Journal of pharmaceutical sciences Vol. 84; no. 7; p. 884
• Main Authors: Caira, M R, Nassimbeni, L R, Timme, M
• Format: Journal Article
• Language: English
• Published: United States 01.07.1995
• Subjects: Acetonitriles - chemistry; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Ethanol - chemistry; Molecular Structure; Piroxicam - analogs & derivatives; Piroxicam - chemistry; Temperature; Thermogravimetry; X-Rays
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600840719

The products of recrystallization of tenoxicam (4-hydroxy-2-methyl-N-2-pyridinyl-2H-thieno[2,3-e]-1,2-thiazine-3- carboxamide 1,1-dioxide) from ethanol and acetonitrile were investigated by thermogravimetric analysis, differential scanning calorimetry, and X-ray diffraction. Recrystallization from ethanol yielded a polymorph designated 1, and recrystallization from acetonitrile gave a solvate 2 with 1:1 stoichiometry. The structures of 1 and 2 were determined by single-crystal X-ray methods. Polymorph 1 is triclinic, space group P1, with Z = 4; solvate 2 is monoclinic, space group P2(1)/n, with Z = 4. In both crystal structures, the tenoxicam molecule exists in the zwitterionic form, adopting a planar conformation that is stabilized by two intramolecular hydrogen bonds (N(+)-H...O and N-H...O-). Tenoxicam molecules associate by N(+)-H...O and C-H...N hydrogen bonding in both crystal structures. Desolvation of 2 yields a polymorph of tenoxicam that is different from polymorph 1. A study of the kinetics of the desolvation of 2 by dynamic thermogravimetry yielded estimates of the activation energy in the range 69-72 kJ.mol-1. From a comparison of experimental and simulated X-ray powder diffraction patterns, neither 1 nor 2 undergoes a polymorphic transition upon grinding. X-ray patterns based on the single-crystal X-ray data for 1 and 2 are presented as reliable references for their identification.