Complexation of flutamide by native and modified cyclodextrins

Abstract

Abstract Complexation of flutamide (FM), the drug used in treatment of prostate cancer, with α‐, β‐ and γ‐ cyclodextrins (CDs), heptakis(2,6‐di‐ O ‐methyl)‐β‐CD (DM‐β‐CD), heptakis(2,3,6‐tri‐ O ‐methyl)‐β‐CD (TM‐β‐CD), 2‐hydroxypropyl‐β‐CD (2HP‐β‐CD) and carboxymethyl‐β‐CD (CM‐β‐CD) was studied. For all CDs the stability constants were determined by the solubility method. UV spectrophotometry and polarography were used in particular cases. The values of the stability constants increased in the order: α‐CD ≈ γ‐CD <β‐CD ≈ CM‐β‐CD <TM‐β‐CD ≈ 2HP‐β‐CD <DM‐β‐CD. For complexes of FM with β‐CD and TM‐β‐CD, the thermodynamic parameters of complexation were determined from the temperature dependence of the corresponding stability constants. For α‐, β‐, γ‐ and TM‐β‐CD, calculations using HyperChem6 software by the MM + force field were carried out to gain some insight into the host–guest geometry. Copyright © 2003 John Wiley & Sons, Ltd.