Passive permeability is one of the key features that determine absorbability and one of the most studied properties in the early phases of drug development.Newly synthesized succinimide derivatives from two different series (1-aryl-3-methylsuccinimides and 1-aryl-3-ethyl-3-methylsuccinimides) with high biological potential have been subjected to estimation of their passive permeability and their association with (a) experimentally obtained anisotropic lipophilicity, (b) in silico-calculated lipophilicity and (c) in silico-predicted permeability and absorbability.Non-cellular-based parallel artificial membrane permeability assay was applied for quantifying their passive permeation, expressed as logP app . Passive permeation was governed by the lipophilicity of the analysed compounds, and anisotropic lipophilicity was related with statistically significant passive transcellular diffusion (r 2 = 0.614, P < 0.001). Moreover, experimentally determined passive permeability, logP app , was statistically significantly associated with both in silico-predicted absorption constant, k a (r 2 = 0.7886, P < 0.001), and human intestinal absorption (HIA) in percentage (r 2 = 0.484, P < 0.001), respectively. However, there was no statistically significant relationship between experimentally obtained permeability on non-cellular-based model and in silico-predicted Caco-2 permeability based on the predictions conducted on two different software. Based on the obtained results, anisotropic systems are promising surrogates for determining lipophilicity, except for compounds with acidic functional groups that are completely ionized under (pH = 7.4).

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