An Artificial Gut/Absorption Simulator: Description, Modeling, and Validation Using Caffeine

Krutika Meena Harish Jain, Hao Helen Hou, Ronald A. Siegel

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The purpose of this study was to develop and validate a simultaneous dissolution and absorption testing tool, the "artificial gut simulator" (AGS), for oral drug formulations. The AGS was constructed using hollow fibers and housed in a 3-mL UV spectrophotometric cuvette that provided a large surface area-to-volume ratio to simulate absorption at a physiological rate. A quasi-steady-state model describing absorption was developed and validated using a high aqueous solubility, BCS-I model compound, caffeine. This model was used to optimize the AGS operating parameters to simulate physiological gastric emptying and caffeine absorption, which was further input into a one-compartment pharmacokinetic (PK) model. The in vivo caffeine plasma concentration-time profiles matched those predicted by the PK model with in vitro input from the AGS. This work provides a framework for establishing an in vitro/in vivo correlation with high-permeability, BCS-II supersaturating drug formulations, which will be explored in the future studies.

Original languageEnglish (US)
Article number87
JournalAAPS Journal
Volume24
Issue number5
DOIs
StatePublished - Sep 2022

Bibliographical note

Funding Information:
This research was funded by Genentech Inc. A Bighley Graduate Fellowship (2017–2019) and a Rowell Fellowship (2018-2019) were awarded to Krutika Harish Jain by the College of Pharmacy, University of Minnesota.

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.

Keywords

  • dissolution
  • in vitro
  • membrane transport
  • oral absorption
  • passive diffusion
  • Gastrointestinal Absorption
  • Administration, Oral
  • Models, Biological
  • Solubility
  • Permeability
  • Intestinal Absorption
  • Caffeine

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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