Simultaneous assessment of in vitro lipolysis and permeation in the mucus-PVPA model to predict oral absorption of a poorly water soluble drug in SNEDDSs

Abstract

The prediction of the <i>in vivo</i> performance of self-nanoemulsifying drug delivery systems (SNEDDSs) is currently gaining increasing attention. Therefore, the need for reliable <i>in vitro</i> models able to assess the drug solubilization capacity of such formulations upon <i>in vitro</i> lipolysis, as well as to concomitantly evaluate <i>in vitro</i> drug permeation, has become ever so evident. In the current study, the high-throughput <i>in vitro</i> intestinal lipolysis model was combined with the mucus-PVPA <i>in vitro</i> permeation model to study the solubilization capacity of SNEDDSs for the poorly water-soluble drug fenofibrate and to study the consequent drug permeation. Moreover, drug solubilization and permeation were evaluated both in the presence and absence of lipolysis. The results obtained demonstrated that the presence of <i>in vitro</i> lipolysis significantly impacted the solubilization and permeation profiles of fenofibrate compared to its absence. The results were in accordance with already published <i>in vivo</i> data regarding the same fenofibrate-loaded SNEDDSs. Additionally, the correlation between the <i>in vitro</i> permeation data and <i>in vivo</i> plasma concentration in rats was found to be excellent both in the presence and absence of lipolysis (R² > 0.98), highlighting the ability of the developed combined <i>in vitro</i> model to predict <i>in vivo</i> drug absorption.