ASSOCIATION OF KETOROLAC TROMETHAMINE IN AQUEOUS SOLUTIONS AND ITS RELATIONSHIP TO SOLUBILIZATION

Abstract

Some physico-chemical properties of aqueous racemic Ketorolac Tromethamine (KT) solutions were measured as a function of concentration (0-1.0 M). These included surface tension, osmolality, partition coefficients and electrical conductivity at different temperatures (10, IS, 20, 25, 30, 40 and 50° C). These measurements indicate that KT undergoes nonmicelar self-association in water. Comparison of thesolubilitiesof spironolactone and diazepam in aqueous KT with the corresponding solubilities in known aqueous hydrotropic agents (sodium benzoate and salicylate) nonmicellar chlorpheniramine maleate (BP grade of  99 % purity) and miceilar chlorpromazine hydrochloride (BP grade of  99 % purity) indicates KT to undergo nonmicellar association, with a capacity for solubilization intermediate between hydrotropic agents and miceilar solubilizers. The solubilities of normal alkanols (C₄-C₁₀ ) were also measured against aqueous KT concentration. Compared with their solubilities in miceilar surfactants (sodium dodecylsulfate and chlorpromazine hydrochloride) aqueous KT appears to be a less efficient solubilizer. Molecular mechanical modeling of intermolecular interactions between KT species in water indicate that trimeric species have lower energies compared with those of the same number of monomeric (or monomeric plus dimeric) entities.