Investigating two complex formations of β−cyclodextrin and γ−cyclodextrin with dexamethasone in terms of stoichiometry and phase-solubility diagrams.

Nadia Korsgaard Hansen, David Bartos, Kasper Larsen, Malene Søgaard Hedebæk Pedersen & Emil Fosgaard Lund

Studenteropgave: Fagmodulprojekt

Abstrakt

Studies have shown that drugs can be made more bioavailable to the human body, by binding in complexes with cyclodextrins. In this project we have examined two types of cyclodextrins; β- and γ-cyclodextrin, and their ability to form complexes with dexamethasone. To examine these abilities we have used High Pressure Liquid Chromatography (HPLC), which will provide the concentration of dexamethasone in our samples, and Nuclear Magnetic Resonance (NMR), which, alongside HPLC, will give rise to a phase-solubility diagram. The phase-solubility diagrams will suggest a binding ratio. Furthermore, Isothermal Titration Calorimetry (ITC) is used to provide a suggested stoichiometry, a binding constant and an enthalpy change. Alongside the ITC, the Van’t Hoff plot is helping to verify if the enthalpy of the formation of complex is temperature dependent or not. These two types of cyclodextrins has been chosen for examination, because β-cyclodextrin previously has been studied thoroughly, meanwhile theory suggest that γ-cyclodextrin could be more effective in optimizing the medical use of dexamethasone, and also on an industrial level, e.g. due to its ability to bind more effectively and that it is degradable in the human body.
Our results show that the formation of complex is larger for γ-cyclodextrin than of β-cyclodextrin. Our results are, however, not sufficient enough to confirm this, and more experiments has to be performed. Our results from ITC show that they bind in a ratio of 1:1, while HPLC and NMR show that dexamethasone binds in the ratio of 2:3 to both γ- and β-cyclodextrin. The Van’t Hoff plot furthermore indicates that ∆H is temperature independent for these binding reactions. Uncertainties, which may be reduced by repeating the experiments, are evident in our results for the solubility of γ-cyclodextrin as well, where HPLC show a concentration of 5 mM and NMR show a concentration of 3.5 mM. Likewise, our results for the solubility of β- and γ-cyclodextrin do not match those of the theory, since our results show a higher solubilty for β-cyclodextrin than for γ-cyclodextrin.

UddannelserKemi, (Bachelor/kandidatuddannelse) Bachelor
SprogEngelsk
Udgivelsesdato19 dec. 2016
Antal sider47
VejledereJens Christian Sidney Schönbeck

Emneord

  • Dexamethasone
  • Cyclodextrin
  • ITC
  • HPLC
  • NMR
  • Van't Hoff