Mechanism of the enhancing effect of glycyrrhizin on nifedipine penetration through a lipid membrane

•Nifedipine forms associates with the natural saponin glycyrrhizin having enhanced solubility and permeability.•PAMPA experiments show a remarkable increase in the amount of nifedipine penetrated in the presence of glycyrrhizin compared to free nifedipine.•MD simulations demonstrate a significant decrease in the energy barrier to the penetration of nifedipine through the lipid bilayer in the presence of glycyrrhizin.•MD simulation shows that the nifedipine/glycyrrhizin complex (1:2) is also able to penetrate the bilayer without prior dissociation.