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

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Ejskjær, Lotte
O'Dwyer, Patrick J.
Ryan, Callum D.
Holm, René
Kuentz, Martin
Box, Karl J.
Griffin, Brendan T.
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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.
Lipid-based formulations , In vitro lipolysis , Fenofibrate , Lipid digestion
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:
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