Developing an in vitro lipolysis model for real-time analysis of drug concentrations during digestion of lipid-based formulations
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Published version
Supplementary materials
Date
2023-12-20
Authors
Ejskjær, Lotte
O'Dwyer, Patrick J.
Ryan, Callum D.
Holm, René
Kuentz, Martin
Box, Karl J.
Griffin, Brendan T.
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Published Version
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.
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Keywords
Lipid-based formulations , In vitro lipolysis , Fenofibrate , Lipid digestion
Citation
Ejskjær, L., O’Dwyer, P.J., Ryan, C.D., Holm, R., Kuentz, M., Box, K.J. and 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. Available at: https://doi.org/10.1016/j.ejps.2023.106681