TY - JOUR

T1 - 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

AU - Falavigna, Margherita

AU - Brurok, Sunniva

AU - Klitgaard, Mette

AU - Flaten, Goril Eide

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - In vivo-in vitro correlation (IVIVC)

KW - In vitro permeation

KW - In vitro lipolysis

KW - Lipid-based formulation

KW - Oral drug delivery

KW - Poorly water-soluble drugs

U2 - 10.1016/j.ijpharm.2021.120258

DO - 10.1016/j.ijpharm.2021.120258

M3 - Journal article

C2 - 33486034

VL - 596

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

M1 - 120258

ER -