The hydroxypropyl–β-cyclodextrin complexation of toltrazuril for enhancing bioavailability
Li Zhang,1,2,* Mengxi Liu,1,* Chaocheng Lu,1 Dandan Ren,1 Guoqing Fan,1 Chang Liu,1 Mengjiao Liu,1 Gang Shu,1 Guangneng Peng,1 Zhixiang Yuan,1 Zhijun Zhong,1 Wei Zhang,1 Hualin Fu1 1Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, China; 2In...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2018-03-01
|
| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/the-hydroxypropyl-beta-cyclodextrin-complexation-of-toltrazuril-for-en-peer-reviewed-article-DDDT |
| _version_ | 1818904791941644288 |
|---|---|
| author | Zhang L Liu MX Lu CC Ren DD Fan GQ Liu C Liu MJ Shu G Peng GN Yuan ZX Zhong ZJ Zhang W Fu HL |
| author_facet | Zhang L Liu MX Lu CC Ren DD Fan GQ Liu C Liu MJ Shu G Peng GN Yuan ZX Zhong ZJ Zhang W Fu HL |
| author_sort | Zhang L |
| collection | DOAJ |
| description | Li Zhang,1,2,* Mengxi Liu,1,* Chaocheng Lu,1 Dandan Ren,1 Guoqing Fan,1 Chang Liu,1 Mengjiao Liu,1 Gang Shu,1 Guangneng Peng,1 Zhixiang Yuan,1 Zhijun Zhong,1 Wei Zhang,1 Hualin Fu1 1Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, China; 2Institute of Traditional Chinese Medicine Pharmacology and Toxicology, Sichuan Academy of Chinese Medicine Sciences, Chengdu, Sichuan, China *These authors contributed equally to this work 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 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. Results: In 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). 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. Keywords: toltrazuril, coccidian, hydroxypropyl–β-cyclodextrin, inclusion complex, pharmacokinetics |
| first_indexed | 2024-12-19T21:13:04Z |
| format | Article |
| id | doaj.art-f84dfd220da7419ba904eca7e2d1827e |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-19T21:13:04Z |
| publishDate | 2018-03-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-f84dfd220da7419ba904eca7e2d1827e2022-12-21T20:05:27ZengDove Medical PressDrug Design, Development and Therapy1177-88812018-03-01Volume 1258358937321The hydroxypropyl–β-cyclodextrin complexation of toltrazuril for enhancing bioavailabilityZhang LLiu MXLu CCRen DDFan GQLiu CLiu MJShu GPeng GNYuan ZXZhong ZJZhang WFu HLLi Zhang,1,2,* Mengxi Liu,1,* Chaocheng Lu,1 Dandan Ren,1 Guoqing Fan,1 Chang Liu,1 Mengjiao Liu,1 Gang Shu,1 Guangneng Peng,1 Zhixiang Yuan,1 Zhijun Zhong,1 Wei Zhang,1 Hualin Fu1 1Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, China; 2Institute of Traditional Chinese Medicine Pharmacology and Toxicology, Sichuan Academy of Chinese Medicine Sciences, Chengdu, Sichuan, China *These authors contributed equally to this work 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 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. Results: In 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). 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. Keywords: toltrazuril, coccidian, hydroxypropyl–β-cyclodextrin, inclusion complex, pharmacokineticshttps://www.dovepress.com/the-hydroxypropyl-beta-cyclodextrin-complexation-of-toltrazuril-for-en-peer-reviewed-article-DDDTToltrazurilcoccidianhydroxypropyl-β-cyclodextrininclusion complexpharmacokinetics |
| spellingShingle | Zhang L Liu MX Lu CC Ren DD Fan GQ Liu C Liu MJ Shu G Peng GN Yuan ZX Zhong ZJ Zhang W Fu HL The hydroxypropyl–β-cyclodextrin complexation of toltrazuril for enhancing bioavailability Drug Design, Development and Therapy Toltrazuril coccidian hydroxypropyl-β-cyclodextrin inclusion complex pharmacokinetics |
| title | The hydroxypropyl–β-cyclodextrin complexation of toltrazuril for enhancing bioavailability |
| title_full | The hydroxypropyl–β-cyclodextrin complexation of toltrazuril for enhancing bioavailability |
| title_fullStr | The hydroxypropyl–β-cyclodextrin complexation of toltrazuril for enhancing bioavailability |
| title_full_unstemmed | The hydroxypropyl–β-cyclodextrin complexation of toltrazuril for enhancing bioavailability |
| title_short | The hydroxypropyl–β-cyclodextrin complexation of toltrazuril for enhancing bioavailability |
| title_sort | hydroxypropyl ndash beta cyclodextrin complexation of toltrazuril for enhancing bioavailability |
| topic | Toltrazuril coccidian hydroxypropyl-β-cyclodextrin inclusion complex pharmacokinetics |
| url | https://www.dovepress.com/the-hydroxypropyl-beta-cyclodextrin-complexation-of-toltrazuril-for-en-peer-reviewed-article-DDDT |
| work_keys_str_mv | AT zhangl thehydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT liumx thehydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT lucc thehydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT rendd thehydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT fangq thehydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT liuc thehydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT liumj thehydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT shug thehydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT penggn thehydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT yuanzx thehydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT zhongzj thehydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT zhangw thehydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT fuhl thehydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT zhangl hydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT liumx hydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT lucc hydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT rendd hydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT fangq hydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT liuc hydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT liumj hydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT shug hydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT penggn hydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT yuanzx hydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT zhongzj hydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT zhangw hydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability AT fuhl hydroxypropylndashbetacyclodextrincomplexationoftoltrazurilforenhancingbioavailability |