title: Chromatographic determination of the association constants between nimesulide and native and modified beta-cyclodextrins.
abstract: The retention of a non-steroidal anti-inflammatory drug (NSAID), i.e. nimesulide, in high performance liquid chromatography (HPLC) was investigated using a phenyl bond silica column and beta-cyclodextrin (beta-CD) or hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as mobile phase additive (0-10 mM). Such a study was carried out in order to determine the most efficient cyclodextrin as a potential drug complexing agent for a future application in pharmaceutical formulation. Assuming a 1:1 stoichiometry, the association constants (K) were calculated from the chromatographic data. At a column temperature of 25 degrees C and in a highly aqueous medium (98% phosphate buffer-2% methanol (v/v)), K was equal to 523 and 1285 M(-1) for the nimesulide-beta-CD and nimesulide HP-beta-CD complexes, respectively. These results were consistent with the data reported previously using phase solubility studies and UV spectrophotometry. As well, the thermodynamic parameters of the inclusion complexes were determined from linear van't Hoff plots for the two inclusion complexes. From the enthalpy and entropy changes, it appeared that nimesulide interact more strongly with HP-beta-CD due to a significant hydrophobic effect between the compound and the flexible hydroxypropyl groups.
authors.affiliation: Laboratoire de Chimie Analytique, UFR de Pharmacie, Domaine de la Merci, 38700 La Tronche, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Ravelet
authors.forename: Annabelle
authors.initials: A
authors.lastname: Geze
authors.forename: Annick
authors.initials: A
authors.lastname: Villet
authors.forename: Catherine
authors.initials: C
authors.lastname: Grosset
authors.forename: Anne
authors.initials: A
authors.lastname: Ravel
authors.forename: Denis
authors.initials: D
authors.lastname: Wouessidjewe
authors.forename: Eric
authors.initials: E
authors.lastname: Peyrin
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000032:analysis*; D005079:Excipients / Q000032:analysis / Q000737:chemistry; D007202:Indicators and Reagents; D013449:Sulfonamides / Q000032:analysis*; D047392:beta-Cyclodextrins
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D005079:Excipients; D007202:Indicators and Reagents; D013449:Sulfonamides; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C031215:betadex; C012655:nimesulide