Evaluation of the methods for the determination of the stability constant of cyclodextrin-chlorambucil inclusion complexes.

The interaction of the antitumor agent chlorambucil (CHL) with three different cyclodextrins (CD), namely methyl-beta CD (Me beta CD) polymer-beta CD (poly-beta CD) and gamma CD, is examined kinetically and spectrophotometrically, monitoring the hydrolysis and the changes in the UV absorbance of CHL respectively, in the presence of increasing concentrations of the examined CD. The stoichiometry coefficient for all the CHL-CD complexes was calculated and found to be 1:1, using the continuous variation method based on the UV data. Also, the stability constant Kst for the CHL-CD complexes was calculated and evaluated using the 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 highest Kst value), probably due to the enhanced hydrophobic character of this derivative.