Format

Send to

Choose Destination
J Pharm Sci. 2018 Jan;107(1):250-256. doi: 10.1016/j.xphs.2017.08.002. Epub 2017 Aug 19.

Assessment of Passive Intestinal Permeability Using an Artificial Membrane Insert System.

Author information

1
Drug Delivery and Disposition, KU Leuven, Gasthuisberg O&N II, Herestraat 49 - Box 921, Leuven 3000, Belgium.
2
Drug Delivery and Disposition, KU Leuven, Gasthuisberg O&N II, Herestraat 49 - Box 921, Leuven 3000, Belgium. Electronic address: Patrick.augustijns@kuleuven.be.

Abstract

Despite reasonable predictive power of current cell-based and cell-free absorption models for the assessment of intestinal drug permeability, high costs and lengthy preparation steps hamper their use. The use of a simple artificial membrane (without any lipids present) as intestinal barrier substitute would overcome these hurdles. In the present study, a set of 14 poorly water-soluble drugs, dissolved in 2 different media (fasted state simulated/human intestinal fluids [FaSSIF/FaHIF]), were applied to the donor compartment of an artificial membrane insert system (AMI-system) containing a regenerated cellulose membrane. Furthermore, to investigate the predictive capacity of the AMI-system as substitute for the well-established Caco-2 system to assess intestinal permeability, the same set of 14 drugs dissolved in FaHIF were applied to the donor compartment of a Caco-2 system. For 14 drugs, covering a broad range of physicochemical parameters, a reasonable correlation between both absorption systems was observed, characterized by a Pearson correlation coefficient r of 0.95 (FaHIF). Using the AMI-system, an excellent predictive capacity of FaSSIF as surrogate medium for FaHIF was demonstrated (r = 0.96). Based on the acquired data, the AMI-system appears to be a time- and cost-effective tool for the early-stage estimation of passive intestinal permeability for poorly water-soluble drugs.

KEYWORDS:

Caco-2 cells; FaSSIF/FaHIF; apparent permeability coefficient; artificial membrane insert system (AMI-system); intestinal absorption; regenerated cellulose

PMID:
28826878
DOI:
10.1016/j.xphs.2017.08.002
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center