Formation of ion-pairs in aqueous solutions of diclofenac salts

In this work we studied the ability of the diclofenac anion to form ion-pai rs in aqueous solution in the presence of organic and inorganic cations: io n-pairs have a polarity and hydrophobicity more suitable to the partition t han each ion considered separately and can be extracted by a lipid phase. T he cations considered were those of the organic bases diethylamine, diethan olamine, pyrrolidine, N-(2-hydroxyethyl) pyrrolidine and N-(2-hydroxyethyl) piperidine; the inorganic cations studied were Li+, Na+, K+, Rb+, Cs+. Rel ated to each cation we determined the equilibrium constant (k(XD)) for the ion-pair formation with the diclofenac anion in aqueous solution and the wa ter/n-octanol partition coefficient (P-XD) for each type of ion-pair formed . Among the alkali metal cations, only Li+ shows some interaction with the diclofenac anion, in agreement with its physiological behaviour of increasi ng clearance during the administration of diclofenac. The influence of the ionic radius and desolvation enthalpy of the alkali metal cations on the io n-pair formation and partition was briefly discussed. Organic cations promo te the formation of ion-pairs with the diclofenac anion better than the ino rganic ones, and improve the partition of the ion-pair according to their h ydrophobicity. The values of the equilibrium parameters for the formation a nd partition of ion-pairs are not high enough to allow the direct detection of their presence in the aqueous solution. Their formation can be apprecia ted in the presence of a lipid phase that continuously extracts the ion-pai r. Extraction constants (E-XD = P-XD.K-XD) increase passing from inorganic to organic cations. This study could help to clarify the mechanism of the p ercutaneous absorption of diclofenac in the form of a salt, a route where t he formation of ion-pairs appears to play an important role. (C) 1999 Elsev ier Science B.V. All rights reserved.