Successful drug development requires not only the optimization for specific and potent recognition by its pharmacodynamical targets, but also efficient delivery to these target sites. Drug-biomembrane reciprocal interactions are a key determinant to understand how a compound performs at a barrier with relevant implications in its pharmacokinetic behaviour especially in Absorption, Distribution, Metabolism and Excretion (ADME). Concerning this, a rational drug design, where medicinal chemists can envision how a structure can be optimized aiming an improved pharmaceutical profile, can be the solution to avoid bigger investments in drugs that might not be effective. Lipid biomimetic membrane models with different lipid constitution are increasingly employed as alternative platforms with very well defined and controlled conditions to predict structural, biophysical and chemical aspects involved in the compounds’ penetration and/or interaction with biomembranes. As a proof-of-concept, in this study several biomimetic membrane models (cell membrane and epithelial membrane of blood-brain barrier) were used and different biophysical techniques (derivative spectroscopy; quenching of steady-state and time-resolved fluorescence; dynamic light scattering; differential scanning calorimetry and small and wide angle x-ray diffraction) were applied to characterize the pharmacokinetic profile of a newly synthesized drug in order to support drug screening process decisions.