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

Abstract

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 1 H-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)

Interactions between 4-thiothymidine and water-soluble cyclodextrins: Evidence for supramolecular structures in aqueous solutions

“…In other words these protons experienced a more polar surrounding than the ones observed in absence of CD, suggesting that S 4 TdR was partially located near the cavity of 2-HP-α-CD. As reported in [ 57 ] an upfield shift of protons indicates that these protons are close to host atoms rich of π-electrons [ 58 ], which in this case were associated with the oxygen atoms of the CDs, but also reflected some conformational changes produced by the inclusion. Moreover, it is known [ 9 ], that signals of protons located outside the cavity of CDs exhibit an upfield shift, attributable to the C–C bond anisotropy effect.…”

Enhancement of zaleplon oral bioavailability using optimized self-nano emulsifying drug delivery systems and its effect on sleep quality among a sample of psychiatric patients

“…Zaleplon (Zal) is a pyrazolopyrimidine hypnotic drug, prescribed for the short-term management of insomnia. Additionally, it is a potential anticonvulsant which minimizes the convulsions induced by phenylenetetrazole and electroshock by acting on the GABA receptor (Jablan et al., 2011; Janga et al., 2013). Zal is categorized as Class II drugs, according to the bio-pharmaceutical classification system (BCS) (Teixeira et al., 2017; Abd-Elrasheed et al., 2018), showing poor solubility and high permeability which explain its poor dissolution rate, delayed onset of action and limited absorption (Dudhipala, 2016).…”

Development of Eudragit® S100 based pH-responsive microspheres of zaleplon by spray-drying: Tailoring the drug release properties

“…The obtained solution was then diluted to 100 mL by addition of 0.1 M HCl to precipitate the pH-sensitive polymer. After precipitation, aliquots were filtered through 0.45 μm Millipore membrane filter and the drug concentrations in the filtrate were determined spectrophotometrically at 335 nm (Ultrospec Plus, LKB, Pharmacia, Sweden), as described previously [13]. The working range of the method was between 4-40 μm/mL with regression coefficient of 0.9997 and the linear regression equation y = 0.0226x + 0.015.…”

“…A detailed solid state analysis of the microspheres prepared was made in order to validate the effect of the solvent selection on their in vitro drug release characteristics in simulated gastric and intestinal medium and to explain the underlying mechanisms. In the second phase of the research, Eudragit NE30D (E NE30D ), an aqueous dispersion of a neutral copolymer based on ethyl acrylate and methyl methacrylate insoluble in water irrespective of pH, glyceryl monostearate (GMS), a lipophilic surfactant and a randomly methylated β-cyclodextrin (RAMEB), cyclic oligosaccharide able to modify the biopharmaceutical properties of ZAL in solution and in the solid state through the inclusion complex formation [12,13] were used to optimize the release properties of Eudragit microspheres prepared.…”