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Drug permeability profiling using cell-free permeation tools: Overview and applications.

Philippe Berben1, Annette Bauer-Brandl2, Martin Brandl2

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Summary

Cell-free permeation systems offer reliable predictions for passive intestinal absorption, overcoming limitations of cell-based methods. These robust systems are valuable for drug discovery and evaluating non-oral delivery.

Keywords:
Artificial membrane insert system (AMI-system)Oral drug deliveryParallel artificial membrane permeability assay (PAMPA)PermeabilityPermeapad®Phospholipid vesicle-based permeation assay (PVPA)

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Area of Science:

  • Pharmacology
  • Drug Discovery
  • Biophysics

Background:

  • Cell-free permeation systems are emerging as alternatives to cell- or tissue-based assays for predicting passive intestinal absorption.
  • These systems bypass the limitations of traditional methods, offering enhanced reliability and robustness.
  • They are classified into biomimetic (lipid-based) and non-biomimetic (dialysis membrane-based) barriers.

Purpose of the Study:

  • To review and compare available cell-free permeation systems.
  • To evaluate their barrier composition and predictive capacity for intestinal absorption.
  • To highlight their suitability for formulation evaluation and non-oral drug delivery.

Main Methods:

  • Overview of cell-free systems: Parallel Artificial Membrane Permeability Assay (PAMPA), Phospholipid Vesicle-based Permeation Assay (PVPA), Permeapad®, and artificial membrane insert systems (AMI-system).
  • Analysis of barrier composition (biomimetic vs. non-biomimetic).
  • Comparison of predictive capacity against established intestinal permeation models.

Main Results:

  • Cell-free systems demonstrate robustness, maintaining integrity in the presence of food components or excipients.
  • These systems show potential for combined dissolution/permeation evaluation of drug formulations.
  • Their application extends beyond intestinal absorption to non-oral drug delivery by membrane modification.

Conclusions:

  • Cell-free permeation assays provide a reliable and robust method for predicting passive intestinal absorption in drug discovery.
  • Their stability makes them advantageous for formulation assessment and exploring diverse drug delivery routes.
  • These systems represent a significant advancement in permeability profiling.