Comparison of Cellular Monolayers and an Artificial Membrane as Absorptive Membranes in the in vitro Lipolysis-permeation Assay

Abstract

Permeation across Caco-2 cells in lipolysis-permeation setups can predict the rank order of in vivo drug exposure obtained with lipid-based formulations (LBFs). However, Caco-2 cells require a long differentiation period and do not capture all characteristics of the human small intestine. We therefore evaluated two in vitro assays with artificial lecithin-in-dodecane (LiDo) membranes and MDCK cells as absorptive membranes in the lipolysis-permeation setup. Fenofibrate-loaded LBFs were used and the results from the two assays compared to literature plasma concentrations in landrace pigs administered orally with the same formulations. Aqueous drug concentrations, supersaturation, and precipitation were determined in the digestion chamber and drug permeation in the receiver chamber. Auxiliary in vitro parameters were assessed, such as permeation of the taurocholate, present in the simulated intestinal fluid used in the assay, and size of colloidal structures in the digestion medium over time. The LiDo membrane gave a similar drug distribution as the Caco-2 cells and accurately reproduced the equivalent rank-order of fenofibrate exposure in plasma. Permeation of fenofibrate across MDCK monolayers did not, however, reflect the in vivo exposure rankings. Taurocholate flux was negligible through either membrane. This process was therefore not considered to significantly affect the in vitro distribution of fenofibrate. We conclude that the artificial LiDo membrane is a promising tool for lipolysis−permeation assays to evaluate LBF performance.

In Vitro Digestion–In Situ Absorption Setup Employing a Physiologically Relevant Value of the Membrane Surface Area/Volume Ratio for Evaluating Performance of Lipid-Based Formulations: A Comparative Study with an In Vitro Digestion–Permeation Model

“…Recently, in vitro digestion–permeation models with various absorptive membranes (e.g., artificial membranes, cellular monolayers, intestinal tissues, and so on) have increasingly been used to predict the bioperformance of LBFs. − ,, However, most currently used in vitro models generally provide low drug flux (approximately 0.002–0.5% of permeation), , regardless of the membrane type. In some cases, this limitation prevents the evaluation of complex drug absorption processes .…”