Factors governing the dissolution of diclofenac salts

Some factors governing the dissolution for 30 diclofenac salts were examined. The salts were prepared using alkaline metal hydroxides or organic aliphatic bases having linear or cyclic structures and bearing alkyl or hydroxy groups. Each salt was tested by scanning electron microscopy and by calorimetry. The results of dissolution are reported in terms of dissolution efficacy, E(d), as a function of the molecular (chemical structure of the bases), microscopic (morphology of crystals) and macroscopic (solubility of the salts) parameters. All the factors affect E(d) by different amounts: in the case of alkaline metal and methyl amine salts, dissolution appears governed by atomic or molecular parameters (the atomic volume and the number of methyl groups carried by the nitrogen;atom), the morphology of the dissolving particle dominates in the case of the association of elongated crystals. The hydroxy groups, when present in the cation, improve the solubility and E(d) values only to a limited extent, due to the possibility of an internal hydrogen bond, which limits the occurrence of hydrophilicity towards the dissolution medium.