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 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).
Piel
G
G
Laboratoire de Technologie Pharmaceutique, Institut de Pharmacie, Liège, Belgium.
Pirotte
B
B
Delneuville
I
I
Neven
P
P
Llabres
G
G
Delarge
J
J
Delattre
L
L
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D012492:Salts; D013449:Sulfonamides; D014867:Water; D008239:Lysine; C012655:nimesulide