Ex vivo permeability study of poorly soluble drugs across gastrointestinal membranes: acceptor compartment media composition

[Display omitted] •Acceptor compartment media compositions in ex vivo permeability studies for poorly soluble drugs are critically evaluated•An algorithm for selecting solubility-enhancing additives for the acceptor media in ex vivo permeability studies is proposed•The acceptor media components selection is limited by the GIT membrane susceptibility, viability and transport mechanisms•The addition of solubility-enhancing additives to increase the acceptor compartment’s sink conditions was rarely reported Ex vivo drug permeability testing across gastrointestinal (GI) membranes is crucial in drug discovery and oral drug delivery. It is a reliable method for drugs with good solubility, but it poses challenges for poorly soluble drugs, which are common in development pipelines today. Although enabling formulations increase the apparent solubility in the GI compartment (dissolution vessel or permeation chamber’s donor compartment), maintaining solubilized drug in the acceptor compartment during ex vivo testing remains largely unresolved. This review compiles and critically evaluates the diverse compositions of acceptor media used in ex vivo permeability studies for poorly soluble drugs, highlighting this significant yet underexplored aspect of pharmaceutical science. An algorithm is proposed for selecting solubility-enhancing additives for the acceptor media in ex vivo permeability studies of poorly soluble drugs.