Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
Vol. 15, No. 12, 2016, pp. 2675-2682
Bioline Code: pr16352
Full paper language: English
Document type: Research Article
Document available free of charge
Tropical Journal of Pharmaceutical Research, Vol. 15, No. 12, 2016, pp. 2675-2682
© Copyright 2016 - Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria.
19F-nuclear magnetic resonance spectroscopy as a tool to investigate host-guest complexation of some antidepressant drugs with natural and modified cyclodextrins|
Dastjerdi, Leila Shafiee & Shamsipur, Mojtaba
Purpose: 19F-Nuclear magnetic resonance spectroscopy (19F-NMR) was used to study host-guest
complexation of three fluorine containing antidepressant drugs, viz, fluoxetine hydrochloride, citalopram
hydrobromide and fluvoxamine maleate, with various cyclodextrins (CD), including α-, β-cyclodextrin,
methylated α-cyclodextrin (M-α-CD), diamino derivative of methylated α-cyclodextrin, (DAM-α-CD) and
tetramino derivative of methylated α-cyclodextrin (TAM-α-CD).
Methods: Using the mole ratio method, a 1:1 stoichiometry was determined for the resulting inclusion
complexes. 19F chemical shifts were used to determine the formation constant of the complexes.
Experiments were performed with solutions containing 0.001 M drug and various concentrations of CDs.
NMR data were plotted as 19F chemical shift versus CD/drug mole ratio, and fitted using the nonlinear
least-squares curve fitting program, KINFIT, to obtain the formation constant of CD-drug complex.
Molecular modeling (MM) calculations were used to predict the geometry of the complex of fluvoxamine
and β-CD. Molecular modeling studies were performed in vacuum phase, employing empirical force
fields and semi-empirical quantum theory using AM1 Hamiltonian.
Results: Complex formation caused separation of the fluorine peaks that can be assigned to the two
enantiomers of fluoxetine hydrochloride. Molecular modeling data suggest that fluvoxamine/β-CD
inclusion complexes have a 1:1 stoichiometry and that the CF3-substituted ring of fluvoxamine is
embedded in the cavity of β-CD, indicating a good agreement between molecular modeling calculation
and experimental data (NMR data).
Conclusion: One-dimensional 19F-NMR is a fast and convenient method for the determination of
complex stoichiometry and complexation constants of natural and modified CDs and fluorinated drugs.
Antidepressant drugs; Cyclodextrins; Complexation; Inclusion complex; Formation constant; 19F-NMR
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