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

• Published in: Drug design, development and therapy Vol. 12; pp. 583 - 589
• Main Authors: Zhang, Li, Liu, Mengxi, Lu, Chaocheng, Ren, Dandan, Fan, Guoqing, Liu, Chang, Liu, Mengjiao, Shu, Gang, Peng, Guangneng, Yuan, Zhixiang, Zhong, Zhijun, Zhang, Wei, Fu, Hualin
• Format: Journal Article
• Language: English
• Published: New Zealand Taylor & Francis Ltd 01.01.2018; Dove Medical Press
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin - administration & dosage; 2-Hydroxypropyl-beta-cyclodextrin - chemistry; 2-Hydroxypropyl-beta-cyclodextrin - pharmacokinetics; Administration, Oral; Animals; Bioavailability; Biological Availability; Chinese medicine; Chromatography; coccidian; Coccidiosis; Complex formation; Complexation; Cyclodextrins; Female; Fourier transforms; High performance liquid chromatography; hydroxypropyl-β-cyclodextrin; inclusion complex; Infrared spectrophotometers; Kinetics; Laboratory animals; Liquid chromatography; Magnetic resonance spectroscopy; Male; Medical research; Nanoemulsions; NMR; Nuclear magnetic resonance; Oral administration; Original Research; Pharmaceuticals; Pharmacokinetics; Pharmacy; Rabbits; Solubility; Spectrophotometry; Spectrum analysis; Thin layer chromatography; Toltrazuril; Triazines - administration & dosage; Triazines - chemistry; Triazines - pharmacokinetics; β-Cyclodextrin; United States > US; China; pharmacokinetics; inclusion complex; hydroxypropylβ-cyclodextrin; toltrazuril; coccidian
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S157611

Toltrazuril (Tol) is used to prevent and combat coccidiosis. However, its low aqueous solubility and poor oral bioavailability limit clinical application. 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 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. In rabbit plasma, the time to peak concentration ( ) of Tol-HP-β-CD was shorter than that of Tol (12 h vs 24 h). (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 ( ,0.01) than those of the Tol group ( , 8.02±1.04 μg/mL; AUC0-∞, 514.03±66.65 mg/L h). 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.