TY - JOUR

T1 - Predicting Oral Absorption of fenofibrate in Lipid-Based Drug Delivery Systems by Combining In Vitro Lipolysis with the Mucus-PVPA Permeability Model

AU - Falavigna, Margherita

AU - Klitgaard, Mette

AU - Berthelsen, Ragna

AU - Muellertz, Anette

AU - Flaten, Goril Eide

PY - 2021

Y1 - 2021

N2 - The aim of this work was to develop a new in vitro lipolysis-permeation model to predict the in vivo absorption of fenofibrate in self-nanoemulsifying drug delivery systems (SNEDDSs). More specifically, the in vitro intestinal lipolysis model was combined with the mucus-PVPA (Phospholipid Vesicle-based Permeation Assay) in vitro permeability model. Biosimilar mucus (BM) was added to the surface of the PVPA barriers to closer simulate the intestinal mucosa. SNEDDSs for which pharmacokinetic data after oral dosing to rats was available in the literature were prepared, and the ability of the SNEDDSs to maintain fenofibrate solubilized during in vitro lipolysis was determined, followed by the assessment of drug permeation across the mucus-PVPA barriers. The amount of drug solubilized over time during in vitro lipolysis did not correlate with the AUC (area under the curve) of the plasma drug concentration curve. However, the AUC of the drug permeated after in vitro lipolysis displayed a good correlation with the in vivo AUC (R-2 > 0.9). Thus, it was concluded that the in vitro lipolysisemucus-PVPA permeation model, simulating the physiological digestion and absorption processes, was able to predict in vivo absorption data, exhibiting great potential for further prediction of in vivo performance of SNEDDSs. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

AB - The aim of this work was to develop a new in vitro lipolysis-permeation model to predict the in vivo absorption of fenofibrate in self-nanoemulsifying drug delivery systems (SNEDDSs). More specifically, the in vitro intestinal lipolysis model was combined with the mucus-PVPA (Phospholipid Vesicle-based Permeation Assay) in vitro permeability model. Biosimilar mucus (BM) was added to the surface of the PVPA barriers to closer simulate the intestinal mucosa. SNEDDSs for which pharmacokinetic data after oral dosing to rats was available in the literature were prepared, and the ability of the SNEDDSs to maintain fenofibrate solubilized during in vitro lipolysis was determined, followed by the assessment of drug permeation across the mucus-PVPA barriers. The amount of drug solubilized over time during in vitro lipolysis did not correlate with the AUC (area under the curve) of the plasma drug concentration curve. However, the AUC of the drug permeated after in vitro lipolysis displayed a good correlation with the in vivo AUC (R-2 > 0.9). Thus, it was concluded that the in vitro lipolysisemucus-PVPA permeation model, simulating the physiological digestion and absorption processes, was able to predict in vivo absorption data, exhibiting great potential for further prediction of in vivo performance of SNEDDSs. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

KW - Gastrointestinal tract

KW - In vitro/in vivo (IVIVC) correlation

KW - In vitro model

KW - Lipid-based formulation

KW - Oral drug delivery

KW - Permeability

KW - Poorly water-soluble drug

KW - Precipitation

KW - Self-emulsifying

KW - VESICLE-BASED BARRIER

KW - WATER-SOLUBLE DRUGS

KW - PERMEATION ASSAY

KW - VIVO PERFORMANCE

KW - FORMULATIONS

KW - TRANSPORT

KW - EFFICIENT

U2 - 10.1016/j.xphs.2020.08.026

DO - 10.1016/j.xphs.2020.08.026

M3 - Journal article

C2 - 32916137

VL - 110

SP - 208

EP - 216

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 1

ER -