New Orthorhombic Form of 2-[(2,6-Dichlorophenyl)amino]benzeneacetic Acid (Diclofenac Acid)

Abstract

Diclofenac acid, 2-[(2,6-dichlorophenyl)amino]benzeneacetic acid, is a non-steroidal anti-flammatory drug. The structures of two monoclinic forms of diclofenac acid with space groups of P21/c (HD1) and C2/c (HD2) were reported by Castellari and Ottani. 1 In this paper, we report on a new orthorhombic form of diclofenac acid (HD3) with the space group Pcan.Diclofenac sodium, a sodium salt of 2-[(2,6-dichlorophenyl)amino]benzeneacetic acid (2 g) was dissolved in water. The solution was acidified with 1 M HCl until a white precipitate of diclofenac acid was observed. The precipitate was filtered, washed with distilled water and dried in vacuo. The precipitate (HD3) was recrystallized from hot methanol by slow evaporation. X-ray diffraction data were collected at room temperature using a Bruker SMART CCD area detector. The collected data were reduced using SAINT, 2 and an empirical absorption correction was performed using SADABS. 3 A total of 19487 reflections were measured, of which 4267 reflections (R(int) = 0.1079) were unique. The structure was solved by direct methods and refined with anisotropic displacement parameters for all non-hydrogen atoms by full-matrix least-squares using the SHELX-97 package for PC. 4 The coordinates of the hydrogen atoms were calculated from the riding model, except Fig. 2 Molecular structure of diclofenac acid. Thermal ellipsoids are drawn at the 50% probability level.

Diclofenac Salts. V. Examples of Polymorphism among Diclofenac Salts with Alkyl-hydroxy Amines Studied by DSC and HSM

“…All the H-bonds involve the hydrophilic groups inside the dimer inter- and intra-molecularly and therefore make the diclofenac molecule less available to intermolecular interaction with the environment, such as the water molecules of the solvent. This close association causes the high melting point and the poor solubility in water: the molecule does not form hydrates and only polymorphs have been described, with very limited conformational modification with respect to the more stable structure [16,17]. …”

Tris(2-ammonioethyl)amine tris({2-[(2,6-dichlorophenyl)amino]phenyl}acetate) hexahydrate

“…A search of the April 2003 release of the Cambridge Structural Database (Allen, 2002) reveals that the crystal structure of diclofenac acid has been reported five times [Moser et al, 1990;Kovala-Demertzi et al, 1993;Castellari & Ottani, 1997b (2 polymorphic forms); Jaiboon et al, 2001]. Moreover, in attempts to improve the structural characteristics of diclofenac acid, organic salts have been prepared, using small aliphatic bases, and their structures studied.…”

Novel nanosized formulations of two diclofenac acid polymorphs to improve topical bioavailability

“…In both forms molecules are linked to each other through the carboxyl groups giving rise to centrosymmetric dimers (Castellari and Ottani, 1997). Third polymorph is an orthorhombic form (HD3, space group Pcan) where no intermolecular hydrogen bond is present (Jaiboon et al, 2001). In all the forms, a bifurcated intramolecular hydrogen bond involves N-H group.…”