Gastric retention pellets of edaravone with enhanced oral bioavailability: Absorption mechanism, development, and in vitro/in vivo evaluation

Qingguo Li, Wenhai Huang, Juan Yang, Jianfeng Wang, Min Hu, Jianmei Mo, Yuzhu Cheng, Zhanlun Ou, Zhenyu Zhang, Shixia Guan

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3 Citations (Scopus)
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Abstract

Absorption mechanism of edaravone (EDR) was studied to inform the preparation of gastric retention pellets with the aim to enhance its oral bioavailability. Three different models, namely, Caco-2 cells model, in situ single-pass intestinal perfusion model, and everted gut sac model in rats, were employed to characterize the gastrointestinal absorption kinetics of EDR. And it was found that passive transfer plays a vital role for the transport of EDR, and acidic condition is preferable for EDR absorption. Further, it is likely that EDR acts as a substrate for P-glycoprotein and multidrug-resistance protein. And hence, an orally available gastric retention pellets were developed accordingly. Pharmacokinetic experiments performed with rats and beagles showed that the absolute bioavailability of EDR solution and enteric-coated pellets following oral administration were 33.85% ± 2.45% and 7.64% ± 1.03%, indicating that stomach absorption is better than intestinal adsorption for EDR. However, the gastric retention pellets resulted in 68.96% absolute bioavailability and about 200% relative bioavailability in comparison to EDR solution, which was 9 times that of enteric-coated pellets. The present work demonstrates that gastric retention pellets has excellent potential as oral administration route for EDR.
Original languageEnglish
Pages (from-to)62-69
JournalEuropean Journal of Pharmaceutical Science
Volume119
Early online date6 Apr 2018
DOIs
Publication statusPublished - 1 Jul 2018

Keywords

  • edaravone
  • high density gastric retention pellets
  • pH dependent
  • absorption mechanism
  • oral bioavailability

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