Complexation of flutamide by native and modified cyclodextrins

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.

Effect of 2-Hydroxypropyl-β-cyclodextrin on Solubility of Sparingly Soluble Drug Derivatives of Anthranilic Acid

“…Glibenclamide has extremely poor aqueous solubility and resulting low bioavailability, thus to improve its capability the complexes with 2HP- β -CD were also presented [ 11 ]. The values of stability constants of flutamide-2HP- β -CD were very high in comparison with five other CDs [ 12 ] and lower for the complexation of ketoconazole-2HP- β -CD [ 13 ].…”

Association Mechanism of S-Dinitrophenyl Glutathione with Two Glutathione Peroxidase Mimics: 2, 2¢-Ditelluro- and 2, 2¢-Diseleno-bridged b-cyclodextrins

“…Stabilization energy (Δ E ) upon complexation was calculated for the minimum energy structure according to eq . 5 [ 29 , 30 ]: ΔE = E complex − (E host + E guest ) …”

Supramolecular Nanoscaled Self‐Assembly of Bifunctional Cyclodextrin and Trifunctional Melamine Precursors

“…Because this hybrid computational method allows a combination of methods such as QM/QM or QM/MM, any inclusion formation involving CDs can differentiate between environment effects stemming from the CDs by the QM or MM method and the chemistry of the guest molecules by QM or MM method, respectively. The binding energy based on the ONIOM analysis upon inclusion complexation among the three β ‐CDs and TPA and calculated for the minimum energy structure are defined according to the following equation:29, 30 where E complex , E TPA , and E β ‐CDs represent the total optimized energy of the complex, the free TPA, and the free β ‐CDs. Table 1 summarizes the results of the theoretical calculations, which were carried out in the gas phase without considering solvation effects.…”