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

INTRODUCTION: Toltrazuril (Tol) is used to prevent and combat coccidiosis. However, its low aqueous solubility and poor oral bioavailability limit clinical application. METHODS: To 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 (1)H 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. RESULTS: In rabbit plasma, the time to peak concentration (T(max)) of Tol-HP-β-CD was shorter than that of Tol (12 h vs 24 h). C(max) (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 (C(max), 8.02±1.04 μg/mL; AUC0-∞, 514.03±66.65 mg/L h). CONCLUSION: It 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.