Improving Solubility and Oral Bioavailability of Febuxostat by Polymer-Coated Nanomatrix

Yi-Fan Yin; Yang Guo; Wen-Ding Song; Xiao-Chuan Duan; Xiu-Chai Zheng; Ting Zhong; Shuang Zhang; Xin Yao; Mei-Qi Xu; Qiang Zhang; Xuan Zhang

doi:10.1208/s12249-017-0905-z

Improving Solubility and Oral Bioavailability of Febuxostat by Polymer-Coated Nanomatrix

AAPS PharmSciTech. 2018 Feb;19(2):934-940. doi: 10.1208/s12249-017-0905-z. Epub 2017 Oct 27.

Authors

Yi-Fan Yin^{1

2}, Yang Guo^{1

2}, Wen-Ding Song^{1

2}, Xiao-Chuan Duan^{1

2}, Xiu-Chai Zheng^{1

2}, Ting Zhong^{1

2}, Shuang Zhang^{1

2}, Xin Yao^{1

2}, Mei-Qi Xu^{1

2}, Qiang Zhang^{1

2

3}, Xuan Zhang^{4

5}

Affiliations

¹ Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
² Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Beijing, 100191, China.
³ State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.
⁴ Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China. xuanzhang@bjmu.edu.cn.
⁵ Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Beijing, 100191, China. xuanzhang@bjmu.edu.cn.

PMID: 29079988
DOI: 10.1208/s12249-017-0905-z

Abstract

Here, the mesoporous silica (Sylysia 350) was selected as mesoporous material, hydroxypropyl methylcellulose (HPMC) was selected as crystallization inhibitor, and febuxostat (FBT) was selected as model drug, respectively. The FBT-Sylysia-HPMC nanomatrix (FBT@SHN) was prepared. The characteristics of FBT@SHN were investigated in vitro and in vivo. Our results indicated that the FBT in FBT@SHN was in amorphous form. The solubility and dissolution of FBT in FBT@SHN were significantly increased. The oral bioavailability of FBT in FBT@SHN was greatly improved 5.8-fold compared with that in FBT suspension. This nanomatrix could be used as a drug delivery platform for improving the oral bioavailability.

Keywords: HPMC; febuxostat; nanomatrix; oral bioavailability.

MeSH terms

Administration, Oral
Animals
Biological Availability
Crystallization
Drug Delivery Systems / methods
Febuxostat / administration & dosage
Febuxostat / chemistry*
Febuxostat / metabolism*
Gout Suppressants / administration & dosage
Gout Suppressants / chemistry
Gout Suppressants / metabolism
Hypromellose Derivatives / administration & dosage
Hypromellose Derivatives / chemistry
Hypromellose Derivatives / metabolism
Male
Methylcellulose / chemistry
Nanostructures / administration & dosage
Nanostructures / chemistry*
Polymers / administration & dosage
Polymers / chemistry*
Polymers / metabolism*
Rats
Rats, Sprague-Dawley
Silicon Dioxide / administration & dosage
Silicon Dioxide / chemistry
Silicon Dioxide / metabolism
Solubility

Substances

Gout Suppressants
Polymers
Febuxostat
Hypromellose Derivatives
Silicon Dioxide
Methylcellulose