Influence of solvent effect on polymorphism of 4-hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide-1, 1-dioxide (piroxicam)

Abstract

Piroxicam (4-hydroxy-2-methyl-N-2-piridyl-2H1,2-benzothiazine-3-carboxamide1,1-dioxide), belongs to the class of acidic, nonsteroidal antiinflammatory (NSAI) drugs (Wiseman et al., 1976). Piroxicam is an effective analgesic agent in rheumatoid arthritis, ankylosing spondylitis, and acute pain in muskuloskeletal disorder and episiotomy. It can diminish or inhibit the development of all symptoms of inflammation no matter what its reason (Brogden et al., 1981). Piroxicam crystallizes in two modifications o~ and/3 (Fig. 1), in space groups Pca21 with Z = 4 and P21/c with Z = 4 (Reck et al., 1988; Kojir-Prodi6 and Ruzir-Toros, 1982), respectively. The conformation of the molecule in both structures is approximately planar and rigid, owing to the strong intramolecular hydrogen bonding O ( 1 7 ) H . . . O ( 1 5 ) of lengths 2.526(2)A (cr and 2.561(5),~ (/3). The crystals with the c~ modification exhibit more or less disorder (Reck et al., 1988) depending on crystallization conditions. The c~ structure is rigid owing to the formation of the infinite chains of the weak bifurcated intermolecular hydrogen bonds O ( 1 7 ) H . . . O ( 1 2 ) of the length 3.007 A,. The free N(16)--H groups have the intermolecular distances close to the van der Waals' (Reck et al., 1988). The/3 structure contains the cyclic dimers with the intermolecular hydrogen bonds N(16)--H 9 9 9 O(11) of