Preparation and characterisation of a range of diclofenac salts

Physicochemical properties of diclofenac salts prepared using eight different counterions and including five novel salts, obtained with the bases 2-amino-2-methyl-1,3-propanediol, 2-amino-2-methylpropanol, tert-butylamine, benzylamine and deanol, were compared. Four of the bases used to prepare these salts were related in their chemical structure, differing only in the number of hydroxy groups. Characterisation techniques included X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, thermomicroscopy, Karl Fischer titration, FT-IR spectroscopy and elemental analysis. In the case of salts prepared from 2-amino-2-methylpropanol and benzylamine, two polymorphic forms of each salt were identified. For the 2-amino-2-methyl-1,3-propanediol salt, a pseudopolymorphic form was identified. The aqueous solubilities of the salts studied ranged from 3.95 mM (tris(hydroxymethyl)aminomethane salt) to 446 mM (deanol salt), corresponding to a 113-fold difference in solubility. The solubility of diclofenac deanol was higher than the solubilities for diclofenac salts reported earlier. Correlation was found between the inverse of the salt melting point and the logarithm of salt solubility. A log-log relationship was observed between salt solubility and hydrogen ion concentration in the salt solution. Relationships between the properties of the salt-forming agents and those of the resulting diclofenac salts were explored. Reasonable correlation was found between the free base melting point and the salt melting point.