Association of Ketorolac Tromethamine in aqueous solutions and its relationship to solubilization

Some physico-chemical properties of aqueous racemic Ketorolac Tromethamine (KT) solutions were measured as a function of concentration (0-1.0 M). Thes e included surface tension, osmolality, partition coefficients and electric al conductivity at different temperatures (10, 15, 20, 25, 30, 40 and 50 de grees C). These measurements indicate that KT undergoes nonmicelar self-ass ociation in water. Comparison of the solubilities of spironolactone and dia zepam in aqueous KT with the corresponding solubilities in known aqueous hy drotropic agents (sodium benzoate and salicylate), nonmicellar chlorphenira mine maleate (BP grade of > 99 % purity) and micellar chlorpromazine hydroc hloride (BP grade of > 99 % purity) indicates KT to undergo nonmicellar ass ociation, with a capacity for solubilization intermediate between hydrotrop ic agents and micellar solubilizers. The solubilities of normal alkanols(C- 4-C-10) were also measured against aqueous KT concentration. Compared with their solubilities in micellar surfactants (sodium dodecylsulfate and chlor promazine hydrochloride), aqueous KT appears to be a less efficient solubil izer. Molecular mechanical modeling of intermolecular interactions between KT species in water indicate that trimeric species have lower energies comp ared with those of the same number of monomeric (or monomeric plus dimeric) entities.