Study of the influence of both cyclodextrins and L-lysine on the aqueous solubility of nimesulide; Isolation and characterization of nimesulide-L-lysine-cyclodextrin complexes

Nimesulide is a nonsteroidal antiinflammatory drug that exhibits a very poor water solubility (0.01 mg.ml(-1)). A nimesulide-beta-cyclodextrin complex prepared according to patent application WO 94/02177 has an aqueous solubility of similar to 16 mg.mL(-1) of nimesulide. A nimesulide-L-lysine salt has also been prepared and increases the aqueous solubility of nimesulide to similar to 5.0-7.5 mg.mL(-1). The purpose of the present study was to investigate the interaction of both cyclodextrins and L-lysine on the aqueous solubility of nimesulide. Nimesulide-L-lysine-beta- or gamma-cyclodextrin complexes were prepared by spray-drying. The inclusion of the nimesulide-L-lysine salt into the cyclodextrin cavity was confirmed by differential scanning calorimetry and proton nuclear magnetic resonance spectroscopy. These complexes offered remarkable aqueous solubility. The incorporation of nimesulide in a nimesulide-L-lysine-beta-cyclodextrin complex increased its water solubility by a factor of 10 at pH 1.5 (0.050 mg.mL(-1) for the complex versus 0.005 mg.mL(-1) for nimesulide), 160 at pH 6.8 (2.373 mg.mL(-1) for the complex versus 0.015 mg.mL(-1) for nimesulide), and 3600 in purified water (36.400 mg.mL(-1) for the complex versus 0.01 mg.mL(-1) for nimesulide).