Diclofenac/N-(2-hydroxyethyl)pyrrolidine: a new salt for an old drug

Twenty-four diclofenac salts were prepared using inorganic and organic, linear and cyclic, hydrophilic and hydrophobic bases and their behaviour in polar and poorly polar solvents was examined. Most salts were found more soluble in 1-octanol than in water, suggesting a fair hydrophobicity of these compounds and their existence as ion pairs in non-polar solvents. The salt diclofenac/N-(2-hydroxyethyl)pyrrolidine (DHEP) is the most soluble of this group in 1-octanol (8.39% w/w) and in water (1.89% w/w), where it displays a surfactant behaviour above 1.44% w/w, which can be considered as a critical micellar concentration. It was possible to study the surface activity of diclofenac only using DHEP, since all other salts of this group are not soluble enough to overcome the critical concentration. The mild detergent properties of DHEP were confirmed by the solubilization of lecithin and the formation of mixed micelles with bile salts: these properties appear very interesting in developing new pharmaceutical forms containing DHEP, as a chemical form for the delivery of the active principle diclofenac.