The hydroxypropyl-β-cyclodextrin complexation of toltrazuril for enhancing bioavailability.

Abstract

IntroductionToltrazuril (Tol) is used to prevent and combat coccidiosis. However, its low aqueous solubility and poor oral bioavailability limit clinical application.MethodsTo overcome the shortcomings, toltrazuril–hydroxypropyl–β-cyclodextrin inclusion complex (Tol-HP-β-CD) was prepared and characterized. The comparative plasma disposition kinetics of Tol was analyzed after a single orally administered dose of 10 mg/kg Tol or Tol-HP-β-CD in rabbits. Solution-stirring method was selected to prepare the inclusion complex. Complex formation was characterized by thin-layer chromatography, Fourier transform infrared spectrophotometry, and 1H nuclear magnetic resonance spectroscopy. In plasma profile, plasma samples were collected between 1 and 10 days following administration. Plasma Tol concentrations were determined by high-performance liquid chromatography.ResultsIn rabbit plasma, the time to peak concentration (Tmax) of Tol-HP-β-CD was shorter than that of Tol (12 h vs 24 h). Cmax (19.92±1.02 μg/mL) and area under the concentration–time curve (AUC0-∞, 1,176.86±70.26 mg/L h) of the Tol-HP-β-CD group significantly increased (p,0.01) than those of the Tol group (Cmax, 8.02±1.04 μg/mL; AUC0-∞, 514.03±66.65 mg/L h).ConclusionIt can be concluded that the Tol-HP-β-CD increased the aqueous solubility and enhanced the oral bioavailability in rabbits. Complexation with HP-β-CD is a feasible way to prepare a rapidly absorbed and more bioavailable Tol oral product.