Inclusion complexation of warfarin withβ-cyclodextrins and its influence on absorption kinetics of warfarin in rat

Karadağ, Ömer; Gök, Elmas; Ateş, İbrahim; Kiran, O; Bozkurt, Atilla

doi:10.1007/bf00707609

Cited by 6 publications

(5 citation statements)

References 14 publications

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“…Table 4 summaries the stability constants that were measured in this report. These values show good agreement with those reported by other methods [4,14,15,24,30]. In each case a 1:1 complex was found to be the dominant product, which also agrees with previous observations made in the literature [4,24,29].…”

Section: Discussionsupporting

confidence: 93%

“…This gave a linear relationship (correlation coefficient = 0.998 for five data points), which suggested that 1:1 binding was occurring between ␤-CD and each of the warfarin enantiomers. Based on the slope and intercept of this graph, the average stability constant for (R)-and (S)-warfarin with ␤-CD was found to be 5.2 ± 0.3 × 10 2 M −1 at pH 7.4 and 37 • C. This was statistically identical to the value of 5.4 ± 0.2 × 10 2 M −1 that has been obtained by fluorimetric measurements [24] and the result of 5.2 ± 0.3 × 10 2 M −1 that has been reported through the use of an alternative HPLC method [4].…”

Section: Binding Of Warfarin To β-Cdsupporting

confidence: 57%

“…One way this solubility can be increased is to add ␤-CD as a complexing agent for warfarin. Previous studies have used a variety of methods to examine the binding of warfarin with cyclodextrins, including fluorimetric measurements [24] and HPLC [4]. In these studies, the results have indicated that only 1:1 complexes form between warfarin and ␤-CD or its derivatives.…”

Section: Binding Of Warfarin To β-Cdmentioning

confidence: 97%

“…Warfarin is a weak acid with a pK a of about 5. It also has a relatively low solubility in an aqueous solvent at pH 7.4, with an upper solubility of approximately 58.4 M [24]. One way this solubility can be increased is to add ␤-CD as a complexing agent for warfarin.…”

Section: Binding Of Warfarin To β-Cdmentioning

confidence: 97%

See 3 more Smart Citations

Characterization of drug interactions with soluble β-cyclodextrin by high-performance affinity chromatography

Chen

Ohnmacht

Hage

2004

Journal of Chromatography A

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Section: Discussionsupporting

confidence: 93%

Section: Binding Of Warfarin To β-Cdsupporting

confidence: 57%

Section: Binding Of Warfarin To β-Cdmentioning

confidence: 97%

Section: Binding Of Warfarin To β-Cdmentioning

confidence: 97%

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Characterization of drug interactions with soluble β-cyclodextrin by high-performance affinity chromatography

Chen

Ohnmacht

Hage

2004

Journal of Chromatography A

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“…Recent studies have also exploited W-CD systems as fluorescent probes and site markers in drug-protein interactions [ 23 , 24 ]. In addition to the fluorescence properties, better understanding of the interactions of W with CDs in the ground and excited states at different pH values should lead, in the future, to better modulation of drugs’ p K a values and open-cyclic switchable properties in solution [ 10 , 11 ] and in different microheterogeneous environments that could advance their analytical separation by electrophoresis [ 15 ] and liquid chromatography [ 25 , 26 ], as well as their formulations [ 27 ] and clinical/biomedical applications [ 28 ]. Our results should, therefore, lead to better understanding of the role of CD on manipulating the open-cyclic switchable structure/function of this anticoagulant drug in ground and excited states.…”

Section: Discussionmentioning

confidence: 99%

Sequestration Effect on the Open-Cyclic Switchable Property of Warfarin Induced by Cyclodextrin: Time-Resolved Fluorescence Study

Al-Dubaili

Saleh

2017

Molecules

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The excited-state lifetimes of the anticoagulant drug warfarin (W) in water and in the absence and presence of methyl-β-cyclodextrins (Me-β-CD) were recorded using time-resolved fluorescence measurements. Selective excitation of the open and cyclic protonated isomers of W were acquired with laser emitting diodes (LED) producing 320 and 280 nm excitation pulses, respectively. Formation of the inclusion complex was checked by UV-visible absorption spectroscopy, and the values of binding constants (2.9 × 103 M–1 and 4.2 × 102 M−1 for protonated and deprotonated forms, respectively) were extracted from the spectrophotometric data. Both absorption and time-resolved fluorescence results established that the interior of the macromolecular host binds preferentially the open protonated form, red shifts the maximum of its absorption of light at ~305 nm, extends its excited-state lifetime, and decreases its emission quantum yield (ФF). Collectively, sequestration of the open guest molecules decreases markedly their radiative rate constants (kr), likely due to formation of hydrogen-bonded complexes in both the ground and excited states. Due to lack of interactions, no change was observed in the excited-state lifetime of the cyclic form in the presence of Me-β-CD. The host also increases the excited-state lifetime and ФF of the drug deprotonated form (W−). These later findings could be attributed to the increased rigidity inside the cavity of Me-β-CD. The pKa values extracted from the variations of the UV-visible absorption spectra of W versus the pH of aqueous solution showed that the open isomer is more acidic in both ground and excited states. The positive shifts in pKa values induced by three derivatives of cyclodextrins: HE-β-CD, Ac-β-CD, and Me-β-CD supported the preferential binding of these hosts to open isomers over cyclic.

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Fluorescence enhancement of warfarin induced by interaction with β‐cyclodextrin

Vasquez

Schultz

et al. 2009

Biotechnology Progress

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Warfarin is the most common agent used for control and prevention of venous as well as arterial thromboembolism (blood clots). In aqueous media, warfarin forms inclusion complexes with a family of cyclic oligosaccharides, alpha, beta, gamma-cyclodextrins (CD). The formation of these complexes results in enhancement of the fluorescence of warfarin. Such spectroscopic changes offer a venue for the development of bioanalytical methodologies for warfarin quantification in biological liquids. We characterized the photophysical properties of warfarin in solvents with varying polarity and viscosity. The fluorescence quantum yield of warfarin correlated: (1) strongly with the solvent viscosity (R = 0.979) and (2) weakly with the solvent polarity (R = 0.118). These findings indicate that it is the change of the viscosity, rather than polarity, of the microenvironment that causes the fluorescence enhancement of warfarin upon binding to beta-CD. Utilizing the observed fluorescence enhancement in fluorescence titration measurements, the binding constants of warfarin to beta-CD were obtained (2.6 x 10(2) M(-1)-3.7 x 10(2) M(-1)). Using multivariable linear analysis, we extracted the stoichiometry of warfarin-beta-CD interaction (1:1).

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Inclusion complexation of warfarin withβ-cyclodextrins and its influence on absorption kinetics of warfarin in rat

Cited by 6 publications

References 14 publications

Characterization of drug interactions with soluble β-cyclodextrin by high-performance affinity chromatography

Characterization of drug interactions with soluble β-cyclodextrin by high-performance affinity chromatography

Sequestration Effect on the Open-Cyclic Switchable Property of Warfarin Induced by Cyclodextrin: Time-Resolved Fluorescence Study

Fluorescence enhancement of warfarin induced by interaction with β‐cyclodextrin

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