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.
Green
A R
AR
College of Pharmacy, University of Iowa, Iowa City 52242.
Guillory
J K
JK
D002626:Chemistry, Pharmaceutical; D002699:Chlorambucil / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000032:analysis*; D003912:Dextrins / Q000032:analysis*; D004337:Drug Carriers; D006868:Hydrolysis; D007700:Kinetics; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013213:Starch / Q000032:analysis*; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D003912:Dextrins; D004337:Drug Carriers; D047392:beta-Cyclodextrins; D002699:Chlorambucil; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; D013213:Starch