Predicting Oral Absorption of fenofibrate in Lipid-Based Drug Delivery Systems by Combining In Vitro Lipolysis with the Mucus-PVPA Permeability Model
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Predicting Oral Absorption of fenofibrate in Lipid-Based Drug Delivery Systems by Combining In Vitro Lipolysis with the Mucus-PVPA Permeability Model. / Falavigna, Margherita; Klitgaard, Mette; Berthelsen, Ragna; Muellertz, Anette; Flaten, Goril Eide.
In: Journal of Pharmaceutical Sciences, Vol. 110, No. 1, 2021, p. 208-216.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
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 -
ID: 256271372