EVALUATION OF THE METHODS FOR THE DETERMINATION OF THE STABILITY CONSTANT OF CYCLODEXTRIN-CHLOROAMBUCIL INCLUSION COMPLEXES

The interaction of the antitumor agent chlorambucil (CHL) with three d ifferent cyclodextrins (CD), namely methyl-beta CD (Me beta CD) polyme r-beta CD (poly-beta CD) and gamma CD, is examined kinetically and spe ctrophotometrically, monitoring the hydrolysis and the changes in the UV absorbance of CHL respectively, in the presence of increasing conce ntrations of the examined CD. The stoichiometry coefficient for all th e CHL-CD complexes was calculated and found to be 1:1, using the conti nuous variation method based on the UV data. Also, the stability const ant K-st for the CHL-CD complexes was calculated and evaluated using t he above mentioned two methods, each one based on linear and nonlinear mathematical models. All studies demonstrate that the interaction of CHL with the methylated derivative (Me beta CD) is stronger (the highe st K-st value), probably due to the enhanced hydrophobic character of this derivative. (C) 1997 Elsevier Science B.V.