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

The prediction of the in vivo performance of self-nanoemulsifying drug delivery systems (SNEDDSs) is currently gaining increasing attention. Therefore, the need for reliable in vitro models able to assess the drug solubilization capacity of such formulations upon in vitro lipolysis, as well as to concomitantly evaluate in vitro drug permeation, has become ever so evident. In the current study, the high-throughput in vitro intestinal lipolysis model was combined with the mucus-PVPA in vitro 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 in vitro lipolysis significantly impacted the solubilization and permeation profiles of fenofibrate compared to its absence. The results were in accordance with already published in vivo data regarding the same fenofibrate-loaded SNEDDSs. Additionally, the correlation between the in vitro permeation data and in vivo plasma concentration in rats was found to be excellent both in the presence and absence of lipolysis (R-2 > 0.98), highlighting the ability of the developed combined in vitro model to predict in vivo drug absorption.

Automated summary

The study combined high-throughput in vitro intestinal lipolysis model with mucus-PVPA in vitro permeation model to investigate the solubilization capacity and drug permeation of SNEDDSs for fenofibrate. Results showed a significant impact of in vitro lipolysis on drug solubilization and permeation profiles. The correlation between in vitro permeation data and in vivo plasma concentration in rats was excellent, indicating the predictive ability of the developed combined in vitro model for in vivo drug absorption.