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

Abstract

Cell-free permeation systems are gaining interest in drug discovery and development as tools to obtain a reliable prediction of passive intestinal absorption without the disadvantages associated with cell- or tissue-based permeability profiling. Depending on the composition of the barrier, cell-free permeation systems are classified into two classes including (i) biomimetic barriers which are constructed from (phospho)lipids and (ii) non-biomimetic barriers containing dialysis membranes. This review provides an overview of the currently available cell-free permeation systems including Parallel Artificial Membrane Permeability Assay (PAMPA), Phospholipid Vesicle-based Permeation Assay (PVPA), Permeapad®, and artificial membrane based systems (e.g. the artificial membrane insert system (AMI-system)) in terms of their barrier composition as well as their predictive capacity in relation to well-characterized intestinal permeation systems. Given the potential loss of integrity of cell-based permeation barriers in the presence of food components or pharmaceutical excipients, the superior robustness of cell-free barriers makes them suitable for the combined dissolution/permeation evaluation of formulations. While cell-free permeation systems are mostly applied for exploring intestinal absorption, they can also be used to evaluate non-oral drug delivery by adjusting the composition of the membrane.

Segmental-Dependent Intestinal Drug Permeability: Development and Model Validation of In Silico Predictions Guided by In Vivo Permeability Values

“…However, its applicability is extremely restricted due to its complexity, high cost, and ethical considerations. Several in vitro and in situ methods were developed for the measurement of permeability, including the parallel artificial membrane permeability assay, [24][25][26][27] everted gut sacs, [28][29][30] Ussing side-by-side diffusion chambers, 12,[31][32][33][34] Caco-2 monolayers, [35][36][37] and intestinal perfusion models for example, the rat single-pass intestinal perfusion (SPIP), [38][39][40][41] and the Doluisio technique. 37,[42][43][44] These methods are now well established and frequently used; yet, to assess segmental-dependent intestinal absorption throughout the GIT, rat intestinal perfusion still remain the most significant experimental method.…”

Evaluating side-by-side diffusion models for studying drug supersaturation in an absorptive environment: a case example of fenofibrate and felodipine

“…In addition, it was more time consuming to work with cell‐based barrier systems, as the cells need to be grown and monitored before, under, and after use . In comparison, artificial membranes, such as the PAMPA membrane, were simpler to work with, but may be considered as a less physiologically relevant permeability barrier as they only account for drug transport by passive diffusion . Therefore, the choice of permeation barrier should always be done based on the specific drug and DDS that need testing.…”

Oromucosal drug delivery: Trends in in-vitro biopharmaceutical assessment of new chemical entities and formulations

“…Artificial barriers may represent attractive alternatives to evaluate permeation as compared to any cell-or tissue-based models as they are less laborious in preparation and are expected to yield more reproducible results since variability typically coming along with biological models is circumvented (Berben et al, 2018). In essence, non-cellular permeation models appear less expensive, readily available and therefore most suitable for screening settings in high throughput formats in order to rank drug substances (drug discovery) and their formulations (early drug development) with respect to their biopharmaceutical performance.…”