Exploring impact of supersaturated lipid-based drug delivery systems of celecoxib on in vitro permeation across Permeapad Ⓡ membrane and in vivo absorption
Loading...
Authors
Ilie, Alexandra Roxana
Author (Corporation)
Publication date
03.07.2020
Typ of student thesis
Course of study
Collections
Type
01A - Journal article
Editors
Editor (Corporation)
Supervisor
Parent work
European Journal of Pharmaceutical Sciences
Special issue
DOI of the original publication
Series
Series number
Volume
152
Issue / Number
Pages / Duration
Patent number
Publisher / Publishing institution
Elsevier
Place of publication / Event location
Edition
Version
Programming language
Assignee
Practice partner / Client
Abstract
Supersaturated lipid-based drug delivery systems have recently been investigated for oral administration for a variety of lipophilic drugs and have shown either equivalent or superior oral bioavailability compared to conventional non-supersaturated lipid-based drug delivery systems. The aim of the present work was to explore supersaturated versus non-supersaturated lipid-based systems at equivalent lipid doses, on in vivo bioavailability in rats and on in vitro permeation across a biomimetic PermeapadⓇ membrane to establish a potential in vivo - in vitro correlation. A secondary objective was to investigate the influence of lipid composition on in vitro and in vivo performance of lipid systems. Results obtained indicated that increasing the celecoxib load in the lipid-based formulations by thermally-induced supersaturation resulted in increased bioavailability for medium and long chain mono-/di-glycerides systems relative to their non-supersaturated (i.e. 85%) reference formulations, albeit only significant for the medium chain systems. Long chain systems displayed higher celecoxib bioavailability than equivalent medium chain systems, both at supersaturated and non-supersaturated drug loads. In vitro passive permeation of celecoxib was studied using both steady-state and dynamic conditions and correlated well with in vivo pharmacokinetic results with respect to compositional effects. In contrast, permeation studies indicated that flux and percentage permeated of supersaturated systems, either at steady-state or under dynamic conditions, decreased or were unchanged relative to non-supersaturated systems. This study has shown that by using two cell-free PermeapadⓇ permeation models coupled with rat-adapted gastro-intestinal conditions, bio-predictive in vitro tools can be developed to be reflective of in vivo scenarios. With further optimization, such models could be successfully used in pharmaceutical industry settings to rapidly screen various prototype formulations prior to animal studies.
Keywords
Drug permeability, Dynamic permeation model, In vivo pharmacokinetics, Steady-state flux, Supersaturated lipid-based drug delivery systems
Subject (DDC)
Event
Exhibition start date
Exhibition end date
Conference start date
Conference end date
Date of the last check
ISBN
ISSN
0928-0987
1879-0720
1879-0720
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
License
Citation
Ilie, A. R., & Kuentz, M. (2020). Exploring impact of supersaturated lipid-based drug delivery systems of celecoxib on in vitro permeation across Permeapad Ⓡ membrane and in vivo absorption. European Journal of Pharmaceutical Sciences, 152. https://doi.org/10.1016/j.ejps.2020.105452