title: 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.
abstract: 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 approximately 16 mg.mL-1 of nimesulide. A nimesulide-L-lysine salt has also been prepared and increases the aqueous solubility of nimesulide to approximately 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).
authors.affiliation: Laboratoire de Technologie Pharmaceutique, Institut de Pharmacie, Liège, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Piel
authors.forename: B
authors.initials: B
authors.lastname: Pirotte
authors.forename: I
authors.initials: I
authors.lastname: Delneuville
authors.forename: P
authors.initials: P
authors.lastname: Neven
authors.forename: G
authors.initials: G
authors.lastname: Llabres
authors.forename: J
authors.initials: J
authors.lastname: Delarge
authors.forename: L
authors.initials: L
authors.lastname: Delattre
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D012492:Salts; D012995:Solubility; D013449:Sulfonamides / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D012492:Salts; D013449:Sulfonamides; D014867:Water; D008239:Lysine; C012655:nimesulide