Heptakis(2,6-di-O-methyl)-beta-cyclodextrin complexation with the antitumor agent chlorambucil

The effects of heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DIMEB) and of beta-cyclodextrin (beta-CD) on the aqueous solubility and stability of chlorambucil (CHL) have been compared. In the presence of 1.3 x 10(-3) M DIMEB, there is a greater than 20-fold increase in the stability of chlorambucil at 37 degrees C, pH 4.13. Aqueous solubility of CHL is increased more than 40-fold in the presence of 1.74 x 10(-2) M DIMEB when the solubility is studied under conditions where degradation is minimized (3.0 degrees C, pH 4.13). In the presence of 1.3 x 10(-3) M beta-CD, there is a fourfold increase in the stability, and with 1.74 x 10(-2) M beta-CD, there is a threefold increase in the aqueous solubility of CHL under similar conditions. Stability constants of the CHL complex with DIMEB were determined kinetically and spectrophotometrically under various experimental conditions assuming 1:1 inclusion complex formation.