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

摘要: Zaleplon (ZAL), N-[3-(3-cyanopyrazolo[1, 5- a]pyrimidin-7-yl)phenyl]-N-ethylacetamide, is a nonbenzodiazepine hypnotic drug of the pyrazolopyrimidine class. In dose 5 to 10 mg, indicated for short term management insomnia.1-2 ZAL also shows potent anticonvulsant activity against electroshock- induced convulsions.3 The lipophilic compound which practically insoluble in water.4 It has been recognised that certain level aqueous solubility required substance be readily delivered cellular membrane, but at same time it enough cross membrane itself. case compounds such as ZAL, dissolution gastrointestinal media often rate-limiting step absorption, thus limiting oral bioavailability drug.5 liver, extensively metabolized into pharmacologically inactive metabolites.3 Low and its significant presystemic metabolism lead rather low about 30%.6 Various formulation techniques can applied overcome drugs without affecting their optimised pharmacological action. Among different approaches enhancing drugs, cyclodextrin (CD) complexation proved one most effective.7 interaction between zaleplon (ZAL) cyclodextrins solutions was investigated by spectrofluorimetric phase studies. Stability constants determined both methods showed among natural cyclodextrins, β-cyclodextrin (βCD) formed stabile complex solubilizing efficiency limited. βCD derivatives, stability solubilisation decreased order: randomly methylated-βCD (RAMEB) > sulphobutylether-βCD (SBEβCD) hydroxypropyl-βCD (HPβCD). inclusion complexes with RAMEB were further characterised 1H-NMR spectroscopy formation confirmed cases. ROESY spectra two binding modes exist simultaneously solution. first mode occurs phenyl ring central cavity via wider rim cone dominant. second pyrazolo[1, a]pyrimidine ZAL.