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Purpose  To evaluate the performance of artificial membranes in  in vitro  lipolysis-permeation assays useful for absorption studies of drugs loaded in lipid-based formulations (LBFs).    Methods  Polycarbonate as well as PVDF filters were treated with hexadecane, or lecithin in  n -dodecane solution (LiDo) to form artificial membranes. They were thereafter used as absorption membranes separating two compartments mimicking the luminal and serosal side of the intestine  in vitro . Membranes were subjected to dispersions of an LBF that had been digested by porcine pancreatin and spiked with the membrane integrity marker Lucifer Yellow (LY). Three fenofibrate-loaded LBFs were used to explore the  in vivo  relevance of the assay.    Results  Of the explored artificial membranes, only LiDo applied to PVDF was compatible with lipolysis by porcine pancreatin. Formulation ranking based on mass transfer in the LiDo model exposed was the same as drug release in single-compartment lipolysis. Ranking based on observed apparent permeability coefficients of fenofibrate with different LBFs were the same as those obtained in a cell-based model.    Conclusions  The LiDo membrane was able to withstand lipolysis for a sufficient assay period. However, the assay with porcine pancreatin as digestive agent did not predict the  in vivo  ranking of the assayed formulations better than existing methods. Comparison with a Caco-2 based assay method nonetheless indicates that the  in vitro in vivo  relationship of this cell-free model could be improved with alternative digestive agents.    Electronic supplementary material  The online version of this article (10.1007/s11095-020-02833-9) contains supplementary material, which is available to authorized users.

Suitability of Artificial Membranes in Lipolysis-Permeation Assays of Oral Lipid-Based Formulations