Fabrication of an aprepitant nanosuspension using hydroxypropyl chitosan to increase the bioavailability

Jinwen Liu; Shuyan Li; Wuliji Ao; Yongji Li; Yingge Xiao; Meirong Bai

doi:10.1016/j.bbrc.2022.09.031

Fabrication of an aprepitant nanosuspension using hydroxypropyl chitosan to increase the bioavailability

Biochem Biophys Res Commun. 2022 Nov 26:631:72-77. doi: 10.1016/j.bbrc.2022.09.031. Epub 2022 Sep 20.

Authors

Jinwen Liu¹, Shuyan Li², Wuliji Ao³, Yongji Li⁴, Yingge Xiao², Meirong Bai⁵

Affiliations

¹ College of Traditional Mongolian Medicine, Inner Mongolia Minzu University, Tongliao, 028000, China; School of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, 150040, China.
² College of Traditional Mongolian Medicine, Inner Mongolia Minzu University, Tongliao, 028000, China.
³ Inner Mongolia Research Institute of Traditional Mongolian Medicine Engineering Technology, Tongliao, 028000, China.
⁴ School of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, 150040, China.
⁵ College of Traditional Mongolian Medicine, Inner Mongolia Minzu University, Tongliao, 028000, China; Key Laboratory of Monglian Medicine Research and Development Engineering, Ministry of Education, Tongliao, 028000, China. Electronic address: baimeirong@imun.edu.cn.

PMID: 36179498
DOI: 10.1016/j.bbrc.2022.09.031

Abstract

Aprepitant has been classified into BCS class IV, which has low permeability and poor water solubility, resulting in low bioavailability. This study focused on improving its permeability and solubility in order to improve the oral bioavailability of aprepitant. Hydroxypropyl chitosan (HPCS) was used as a stabilizer for the nanosuspension and wet milling was utilized for improving aprepitant's bioavailability and solubility. The resulting nanosuspension size was 151 ± 14.5 nm and its zeta potential was 63.5 ± 0.34 Mv. The spectral characteristics (XRPD, DSC, TEM) of the nanosuspension suggested that aprepitant existed in the crystalline form and that nanosuspension had 2-fold higher solubility than aprepitant. Hydroxypropyl chitosan can significantly reduce the TEER of Caco-2 cells and the P_app of the suspension in Caco-2 cells increased by 2.2 times compared with aprepitant. The relative bioavailability of the nanosuspension was 147.7% compared with the commercial capsule.

Keywords: Aprepitant; Bioavailability; Hydroxypropyl Chitosan; Nanosuspension.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Aprepitant
Biological Availability
Caco-2 Cells
Chitosan*
Humans
Nanoparticles* / chemistry
Particle Size
Solubility
Suspensions
Water

Substances

Suspensions
Water
Aprepitant
Chitosan