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Mechanisms of poor oral bioavailability of flavonoid Morin in rats: From physicochemical to biopharmaceutical evaluations.

Authors
  • Li, Jianbo1
  • Yang, Yang1
  • Ning, Erjuan2
  • Peng, Youmei1
  • Zhang, Jinjie3
  • 1 Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, No.40. Daxue Road, Zhengzhou, Henan Province 450052, China. , (China)
  • 2 Biological Developing Center of Henan Academy of Sciences, No.58. Hongzhuan Road, Zhengzhou, Henan Province 450000, China. , (China)
  • 3 School of Pharmaceutical Sciences, Zhengzhou University, No.100. Kexue Road, Zhengzhou, Henan Province 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Publication Date
Feb 01, 2019
Volume
128
Pages
290–298
Identifiers
DOI: 10.1016/j.ejps.2018.12.011
PMID: 30557605
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

We recently reported that the absolute oral bioavailability of flavonoid Morin was extremely low at 0.45%, resulting in unsatisfied therapeutic efficacy in vivo. The present study was aimed to systemically assess the pre-absorption risks of Morin for rationale formulation design. Physicochemical properties of Morin were evaluated using in vitro assays including water solubility and stability in simulated gastric, intestinal fluids, followed by permeability tests in Caco-2 cells. The results suggested that both poor solubility and low membrane permeability were rate-limiting steps for oral absorption of Morin. Pharmacokinetic studies were performed via a series of administration routes in a dual-vein cannulated rat model. In contrast to high bioavailability (92.92%) and negligible metabolites of Morin in intraportal administered rats, Morin exhibited low bioavailability (5.28%) and considerable amount of metabolites in rats following intraduodenal administration, suggested that intestinal first-pass metabolism made a major contribution to its poor oral absorption. Morin-phospholipid complex loaded self-emulsifying drug delivery system (MPC-SENDDS) exhibited comparable plasma concentration of metabolites to parent drug after oral administration, indicated that MPC-SNEDDS failed to bypass first-pass metabolism and therefore showed compromised oral absorption enhancement. The present study could promote the development of more efficient oral formulations of Morin with optimized absorption enhancement. Copyright © 2018 Elsevier B.V. All rights reserved.

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