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.