Developing an in vitro lipolysis model for real-time analysis of drug concentrations during digestion of lipid-based formulations

Type
01A - Journal article
Editors
Editor (Corporation)
Supervisor
Parent work
European Journal of Pharmaceutical Sciences
Special issue
DOI of the original publication
Link
Series
Series number
Volume
194
Issue / Number
Pages / Duration
106681
Patent number
Publisher / Publishing institution
Elsevier
Place of publication / Event location
Edition
Version
Programming language
Assignee
Practice partner / Client
Abstract
Understanding the effect of digestion on oral lipid-based drug formulations is a critical step in assessing the impact of the digestive process in the intestine on intraluminal drug concentrations. The classical pH-stat in vitro lipolysis technique has traditionally been applied, however, there is a need to explore the establishment of higher throughput small-scale methods. This study explores the use of alternative lipases with the aim of selecting digestion conditions that permit in-line UV detection for the determination of real-time drug concentrations. A range of immobilised and pre-dissolved lipases were assessed for digestion of lipid-based formulations and compared to digestion with the classical source of lipase, porcine pancreatin. Palatase® 20000 L, a purified liquid lipase, displayed comparable digestion kinetics to porcine pancreatin and drug concentration determined during digestion of a fenofibrate lipid-based formulation were similar between methods. In-line UV analysis using the MicroDISS ProfilerTM demonstrated that drug concentration could be monitored during one hour of dispersion and three hours of digestion for both a medium- and long-chain lipid-based formulations with corresponding results to that obtained from the classical lipolysis method. This method offers opportunities exploring the real-time dynamic drug concentration during dispersion and digestion of lipid-based formulations in a small-scale setup avoiding artifacts as a result of extensive sample preparation.
Keywords
Project
Event
Exhibition start date
Exhibition end date
Conference start date
Conference end date
Date of the last check
ISBN
ISSN
0928-0987
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
Gold
License
'https://creativecommons.org/licenses/by/4.0/'
Citation
Ejskjær, L., O’Dwyer, P. J., Ryan, C. D., Holm, R., Kuentz, M., Box, K. J., & Griffin, B. T. (2024). Developing an in vitro lipolysis model for real-time analysis of drug concentrations during digestion of lipid-based formulations. European Journal of Pharmaceutical Sciences, 194, 106681. https://doi.org/10.1016/j.ejps.2023.106681