Simultaneous assessment of in vitro lipolysis and permeation in the mucus-PVPA model to predict oral absorption of a poorly water soluble drug in SNEDDSs

Margherita Falavigna, Sunniva Brurok, Mette Klitgaard, Goril Eide Flaten*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

11 Citations (Scopus)
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Abstract

The prediction of the in vivo performance of self-nanoemulsifying drug delivery systems (SNEDDSs) is currently gaining increasing attention. Therefore, the need for reliable in vitro models able to assess the drug solubilization capacity of such formulations upon in vitro lipolysis, as well as to concomitantly evaluate in vitro drug permeation, has become ever so evident. In the current study, the high-throughput in vitro intestinal lipolysis model was combined with the mucus-PVPA in vitro permeation model to study the solubilization capacity of SNEDDSs for the poorly water-soluble drug fenofibrate and to study the consequent drug permeation. Moreover, drug solubilization and permeation were evaluated both in the presence and absence of lipolysis. The results obtained demonstrated that the presence of in vitro lipolysis significantly impacted the solubilization and permeation profiles of fenofibrate compared to its absence. The results were in accordance with already published in vivo data regarding the same fenofibrate-loaded SNEDDSs. Additionally, the correlation between the in vitro permeation data and in vivo plasma concentration in rats was found to be excellent both in the presence and absence of lipolysis (R-2 > 0.98), highlighting the ability of the developed combined in vitro model to predict in vivo drug absorption.

Original languageEnglish
Article number120258
JournalInternational Journal of Pharmaceutics
Volume596
Number of pages9
ISSN0378-5173
DOIs
Publication statusPublished - 2021

Keywords

  • In vivo-in vitro correlation (IVIVC)
  • In vitro permeation
  • In vitro lipolysis
  • Lipid-based formulation
  • Oral drug delivery
  • Poorly water-soluble drugs

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