Original scientific paper

https://doi.org/10.5562/cca1800

Stability and Structure of Inclusion Complexes of Zaleplon with Natural and Modified Cyclodextrins

Jasna Jablan ; Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10000 Zagreb, Croatia
Tin Weitner ; Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10000 Zagreb, Croatia
Mario Gabričević ; Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10000 Zagreb, Croatia
Mario Jug ; Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10000 Zagreb, Croatia

Abstract

The interaction between zaleplon (ZAL) and different cyclodextrins in aqueous solutions was
investigated by spectrofluorimetric and phase solubility studies. Stability constants determined by both
methods showed that among natural cyclodextrins, β-cyclodextrin (βCD) formed the most stabile complex
but its solubilizing efficiency was limited. Among βCD derivatives, the complex stability and solubilisation
efficiency decreased in order: randomly methylated-βCD (RAMEB) > sulphobutylether-βCD
(SBEβCD ) > hydroxypropyl-βCD (HPβCD). The inclusion complexes of ZAL with βCD and RAMEB
were further characterised by 1H-NMR spectroscopy and the inclusion complex formation was confirmed
in both cases. ROESY spectra showed two binding modes between ZAL and βCD which exist simultaneously
in the solution. The first binding mode occurs by the inclusion of the phenyl ring of ZAL into the
βCD central cavity via the wider rim of the cyclodextrin cone and is dominant. The second one is formed
by the inclusion of pyrazolo[1,5-a]pyrimidine ring of ZAL.(doi: 10.5562/cca1800)

Keywords

Cyclodextrins; Zaleplon; Inclusion Complexes; Stability Constants; Fluorescence; 1H-NMR

Hrčak ID:

71979

URI

https://hrcak.srce.hr/71979

Publication date:

3.10.2011.

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