In this study, we proposed formulations of diminazene aceturate (DA) designed to improve\nits bioavailability and to maximize the therapeutic index in animals by overcoming the rapid\ndegradation under the acidic pH of the stomach. An important consequence is the fact that its amount\nin the bloodstream is close to the administered dose. This was made possible by incorporating DA\ninto the Beta-cyclodextrinâ??s (BetaCD) cavity in a molar ratio of 1:1. The structure of the resulted inclusion\ncomplex was established by Raman, DSC, andWide-Angle X ray DiBetaraction (WAXD) in solid state\nand by 1H-NMR and H-H ROESY in aqueous solutions. The stoichiometry of the DA:BetaCD inclusion\ncomplex was obtained by using the continuous variation method (Jobâ??s plot), considering the chemical\nshifts variations of protons from both DA and BetaCD compounds in 1H-NMR spectra. The biological\nactivity was estimated in vitro by antioxidant activity and in vivo by comparing the bioavailability of\nparent DA and its inclusion complexes after a single dose administration in Wistar rats by using the\nHPLC method on their blood plasma. In vitro tests showed an improved antioxidant activity. In vivo\ntests have shown that the DA concentration is always much higher in blood plasma of rats when\nDA:BetaCD inclusion complex of 1:1 molar ratio was administered (i.e., at 60 min, DA is around 11 and\n3 times higher when DA:BetaCD inclusion complex of 1:1 molar ratio was administered than the parent\nDA one and DA:BetaCD lyophilized mixture of 1:2 molar ratio, respectively).
Loading....