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A variety of enabling formulations has been developed to address poor oral drug absorption caused by insufficient dissolution in the gastrointestinal tract. As the in vivo performance of these formulations is a result of a complex interplay between dissolution, digestion and permeation, development of suitable in vitro assays that captures these phenomena are called for. The enabling-absorption (ENA) device, consisting of a donor and receiver chamber separated by a semipermeable membrane, has successfully been used to study the performance of lipid-based formulations. In this work, the ENA device was prepared with two different setups (a Caco-2 cell monolayer and an artificial lipid membrane) to study the performance of a lipid-based formulation (LBF), an amorphous solid dispersion (ASD) and the potential benefit of combining the two formulation strategies. An in vivo pharmacokinetic study in rats was performed to evaluate the in vitro-in vivo correlation. In the ENA, high drug concentrations in the donor chamber did not translate to a high mass transfer, which was particularly evident for the ASD as compared to the LBF. The solubility of the polymer used in the ASD was strongly affected by pH-shifts in vitro, and the ph_dependence resulted in poor in vivo performance of the formulation. The dissolution was however increased in vitro when the ASD was combined with a blank lipid-based formulation. This beneficial effect was also observed in vivo, where the drug exposure of the ASD increased significantly when the ASD was co-administered with the blank LBF. To conclude, the in vitro model managed to capture solubility limitations and strategies to overcome these for one of the formulations studied. The correlation between the in vivo exposure of the drug exposure and AUC in the ENA was good for the non pH-sensitive formulations. The deconvoluted pharmacokinetic data indicated that the receiver chamber was a better predictor for the in vivo performance of the drug, however both chambers provided valuable insights to the observed outcome in vivo. This shows that the advanced in vitro setting used herein successfully could explain absorption differences of highly complex formulations.