Preparation And Characterization Of Norfloxacin-sulfobutylether-β-cyclodextrin Complex

Objective To investigate the effect of electrostatic force on complexation of norfloxacin(NFX) with sulfobutylether-β-cyclodextrin(SBE-β-CD) in aqueous solution and further explore its complexing mechanism; To prepare NFX- SBE-β-CD solid complex, then evaluate its in vitro and in vivo characteristics such as solubility,dissolution rate and chemical stability, pharmacokinetics and bioavailability in rats and humans. Methods The UV absorption spectra of NFX, phase solubility diagram, complex stability constant, thermodynamic parameter, and 13C NMR spectra for the drug complexation with SBE-β-CD in aqueous solutions were determined under acid, neutral and alkaline pHs, respectively. The ideal moalr ratio and preparing process of NFX-SBE-β-CD complex was first studied, the complex was then prepared by lyophilization method and identifiedd by infrared spectroscopy (IR), X-ray diffraction and differential scanning calorimetry (DSC). Finally, the solubility, dissolution rate, chemical stability, in vivo pharmacokinetics and bioavailability of the complex were studied. Results The UV spectra of NFX, phase solubility diagram, complex stability constant were obvious different between above three different pHs, but the thermodynamic parameter values such as△G,△H and△S were all negative, indicating that the mechanisms for the complexation process seemed to be same. The optimal host -guest molar ratio was 1:1 and the formation of NFX-SBE-β-CD complex was confirmed in solid state. The solubility, dissolution rate, and chemical stability of NFX were obviously improved due to complexation by SBE-β-CD. Meanwhile, compared with intact drug, in vivo absorption rate and especially bioavailability of the NFX complex were also significantly increased(p<0.05). Conclusion For the charged cyclodextrin derivatives and ionized drugs, electrostatic effect will exert an imprtant influence on the complexation process. SBE-β-CD could significantly enhance the solubility, dissolution rate, chemical stability and bioavailability of NFX, indicating probably better clinical antibiotic effect of the drug.