Physiochemical studies of diclofenac salts and the effect of basis excipients on their dissolution

Abstract

This study involved investigation of the physicochemical properties of diclofenac salts prepared from a range of organic bases. The salts examined included five novel salts of diclofenac, prepared from the following bases: tert-butylamine, 2-amino-2-methylpropanol, 2-amino-2-methyl-1,3- propanediol, benzylamine and deanol. Characterisation techniques included X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, thermal microscopy, Karl Fischer titration, FT-IR spectroscopy and elemental analysis. In the case of the salts prepared from 2-amino-2-methylpropanol and benzylamine, two polymorphic forms of each salt were identified. For three of the salts, novel pseudopolymorphic forms were identified. The behaviour in solution of the novel hydrates of diclofenac N-(2- hydroxyethyl)pyrrolidine and diclofenac diethylamine (DDEA) was investigated. The solubility of the anhydrous form of DDEA was estimated from the ratio of the intrinsic dissolution rates of the monohydrate and anhydrate forms.