Inclusion complexation of diclofenac with natural and modified cyclodextrins explored through phase solubility, 1H-NMR and molecular modeling studies

Abdoh, A. A.; Zughul, Mohammad B.; Davies, J. Eric D.; Badwan, Adnan A.

doi:10.1007/s10847-006-9241-8

Cited by 15 publications

(6 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The positive shift in pK a1 value clearly indicates a lowering in acidity of carboxylic group upon complexation. The similar effect of inclusion complex formation on pK a value has been previously reported [31,32]. The change in the pK a1 value observed in case of HLEV-b-CD is suggesting partial or complete inclusion of the part of the drug molecule responsible to the ionization into b-CD cavity.…”

Section: Influence Of the Inclusion Complex Formation On The Levofloxsupporting

confidence: 85%

Study of inclusion complex of β-cyclodextrin and levofloxacin and its effect on the solution equilibria between gadolinium(III) ion and levofloxacin

et al. 2015

View full text Add to dashboard Cite

The formation of host-guest inclusion complex of levofloxacin with b-cyclodextrin (b-CD) was studied by fluorescence spectroscopy in buffer solution (pH 7.4) at 298 K. The experimental results confirmed the existence of 1:1 inclusion complex of levofloxacin with b-CD. The association constant of the b-CD inclusion complex was obtained from the Benesi-Hildebrand equation. The formation of the inclusion complex was confirmed by the IR and 1 H NMR technique. The complex formation equilibria between Gd(III) ion and levofloxacin were investigated in aqueous solutions without and in the presence of b-cyclodextrin. The stoichiometry and stability constants of the formed complexes are reported, and the concentration distribution of the various complex species has been evaluated as a function of pH. The effect of b-cyclodextrin on dissociation constants, K a , of levofloxacin and stability constants of gadolinium(III)-levofloxacin complexes, b p,q,r , were examined. Furthermore, effect of levofloxacin on the speciation and distribution Gd(III) in human blood plasma was evaluated by computer simulation. Graphical abstract

show abstract

Section: Influence Of the Inclusion Complex Formation On The Levofloxsupporting

confidence: 85%

Study of inclusion complex of β-cyclodextrin and levofloxacin and its effect on the solution equilibria between gadolinium(III) ion and levofloxacin

et al. 2015

View full text Add to dashboard Cite

show abstract

“…A likely explanation would be that the enhanced dissociation of DF improved the solubility of the chelate complex itself. Addition of cyclodextrin, in the absence of zinc ions, resulted in a linear increase in equilibrium solubility of DF-Na with an estimated binding constants in the range 117-574 M À1 , which goes in line with the reported generally low, and variable binding constants of DF to cyclodextrins 3,13,14,17 . Even in the presence of zinc ions, which decreased the solubility of DF-Na five folds at pH 4.5, addition of HPbCD improved the equilibrium solubility of DF-Na, yet with a higher binding constant.…”

Section: Phase Solubility Studies Of Df-na With Hpbcdsupporting

confidence: 85%

“…Comparing the profiles of DF-Na and its HPbCD complex in the absence of zinc, the mean values of AUC (0-1) and Cp/AUC (0-1) of free DF-Na were higher, than those obtained from DF-HPbCD, but not to a statistically significant level, indicating that inclusion complexation to HPbCD did not improve the rate or extent of DF-Na absorption (p40.05). In spite of many literature reports that studied the binding of diclofenac to cyclodextrins, with some of them demonstrating potential enhancement of solubility through inclusion complex formation 3,7,13 , no studies (to the best of our knowledge) have been reported demonstrating the in vivo effect of cyclodextrin complexes which would reflect the oral bioavailability of the drug. Using silicone membranes, it has been demonstrated that cyclodextrins enhanced the flux of diclofenac through the artificial membrane in vitro 6 .…”

Section: In Vivo Pharmacokinetic Studiesmentioning

confidence: 93%

“…However, NSAIDs in general, including DF, suffer from GIT irritations as major side effects at the therapeutic level 1 . At the pharmaceutical level however, DF free acid is known for its poor water solubility, which might lead to delay in its absorption from GIT with the consequent delay in onset of action and in some cases overall bioavailability [2][3][4] . Some methods have been attempted to improve the solubility of DF and DF-Na, with the hope of improving dissolution and therapeutic effects [5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

“…The use of cyclodextrins as solubilizers that improve dissolution, consequently bioavailability and onset of action, is a particularly attractive approach [6][7][8][9][10] . Several previous studies have discussed the inclusion complexes of DF and DF-Na with cyclodextrins 3,6,7,[11][12][13][14][15][16][17] , which were found to improve the in vitro dissolution of diclofenac. However, to the best of our knowledge, there have been no studies that assessed the in vivo bioavailability of DF from its cyclodextrin complexes.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Potential interaction between zinc ions and a cyclodextrin-based diclofenac formulation

Hamdan

El-Sabawi

Jalil

2015

Drug Development and Industrial Pharmacy

View full text Add to dashboard Cite

Complexes of diclofenac sodium (DF-Na) with hydroxypropyl betacyclodextrin (HPβCD) were prepared by co-evaporation in a 1:1 ratio and characterized in light of previously reported data. Phase solubility diagrams were obtained for DF-Na with HPβCD in the presence and absence of zinc ions. Dissolution profiles were obtained for DF-Na and its HPβCD complex at acidic (pH 1.2) as well as in phosphate buffer (pH 6.8), in the presence and absence of zinc. HPβCD, as expected, was shown to improve the dissolution of DF-Na in acidic medium but not in phosphate buffer (pH 6.8). The presence of zinc ions decreased the in vitro dissolution of DF-HPβCD complex in acidic medium (pH 1.2) but not in phosphate buffer (pH 6.8). It was confirmed that the precipitate that was formed by zinc ions in the presence of HPβCD and DF-Na contained no cyclodextrin and most likely it was a mixture of the complexes: DF-Zn and DF-Zn with some molecules of water. In vivo experiments on rats have shown that HPβCD has no statistically significant effect on absorption or bioavailability of DF-Na in spite of the observed improvement of its in vitro dissolution by HPβCD. Moreover, zinc ions were shown to decrease the absorption rate of DF-Na in rats model but did neither significantly alter the absorption nor bioavailability of DF-HPβCD complex. The zinc induced precipitates of DF were shown to have significantly different crystalline properties when HPβCD was present. Therefore, the pharmaceutical details of a DF-Na preparation should be considered when designing the formulation and predicting possible interaction between DF-Na (or other potential NSAIDs) and zinc metal.

show abstract

The pH-dependent complexation between risperidone and hydroxypropyl-β-cyclodextrin

Jug

Kos

Bećirević‐Laćan

2009

J Incl Phenom Macrocycl Chem

View full text Add to dashboard Cite

Inclusion complexation of diclofenac with natural and modified cyclodextrins explored through phase solubility, 1H-NMR and molecular modeling studies

Cited by 15 publications

References 20 publications

Study of inclusion complex of β-cyclodextrin and levofloxacin and its effect on the solution equilibria between gadolinium(III) ion and levofloxacin

Study of inclusion complex of β-cyclodextrin and levofloxacin and its effect on the solution equilibria between gadolinium(III) ion and levofloxacin

Potential interaction between zinc ions and a cyclodextrin-based diclofenac formulation

The pH-dependent complexation between risperidone and hydroxypropyl-β-cyclodextrin

Contact Info

Product

Resources

About