NMR studies of the inclusion complex between β-cyclodextrin and paroxetine

A H-1 and C-13 NMR study on the inclusion complex of paroxetine with beta-cyclodextrin was carried out in order to define the stoichiornetry of the association and its strength. Proton and carbon chemical shift measurements of paroxetine and beta-cyclodextrin were performed a, several molar ratios and temperatures, allowing the determination of a 1:1 stoichiometry and an association constant value of the order of 2 x 10(3) for the paroxetine-beta-cyclodextrin complex. Overhauser effects in the rotating frame were also measured, and the experimental interproton distance constraints have been used for molecular model building of the complex. The obtained model indicates that the benzodioxolyl moiety of paroxetine is deeply inserted in the cavity of the cylindrical structure of p-cyclodextrin, while the fluoro-phenyl ring lays above the wider rim. (C) 2004 Published by Elsevier B.V.