Pharmaceutical Research

, Volume 33, Issue 4, pp 970–982 | Cite as

A new in vitro lipid digestion – in vivo absorption model to evaluate the mechanisms of drug absorption from lipid-based formulations

  • Matthew F. Crum
  • Natalie L. Trevaskis
  • Hywel D. Williams
  • Colin W. Pouton
  • Christopher J. H. Porter
Research Paper



In vitro lipid digestion models are commonly used to screen lipid-based formulations (LBF), but in vitro-in vivo correlations are in some cases unsuccessful. Here we enhance the scope of the lipid digestion test by incorporating an absorption ‘sink’ into the experimental model.


An in vitro model of lipid digestion was coupled directly to a single pass in situ intestinal perfusion experiment in an anaesthetised rat. The model allowed simultaneous real-time analysis of the digestion and absorption of LBFs of fenofibrate and was employed to evaluate the influence of formulation digestion, supersaturation and precipitation on drug absorption.


Formulations containing higher quantities of co-solvent and surfactant resulted in higher supersaturation and more rapid drug precipitation in vitro when compared to those containing higher quantities of lipid. In contrast, when the same formulations were examined using the coupled in vitro lipid digestion – in vivo absorption model, drug flux into the mesenteric vein was similar regardless of in vitro formulation performance.


For some drugs, simple in vitro lipid digestion models may underestimate the potential for absorption from LBFs. Consistent with recent in vivo studies, drug absorption for rapidly absorbed drugs such as fenofibrate may occur even when drug precipitation is apparent during in vitro digestion.


absorption drug solubilisation in situ intestinal perfusion lipid-based drug delivery systems supersaturation 



4-bromophenylboronic acid


Area under the curve




High performance liquid chromatography


Lipid-based formulation


Lipid Formulation Classification System


Sodium taurodeoxycholate




Tributyrin units


Ultra performance liquid chromatography – tandem mass spectrometer



The authors would like to thank Mr Doron Gafni for drawing of the model schematic. Funding support from the Monash University Institute of Graduate Research (MIGR) is gratefully received.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Matthew F. Crum
    • 1
  • Natalie L. Trevaskis
    • 1
  • Hywel D. Williams
    • 1
    • 2
  • Colin W. Pouton
    • 1
  • Christopher J. H. Porter
    • 1
    • 3
  1. 1.Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleAustralia
  2. 2.Capsugel R&D Australia, Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleAustralia
  3. 3.ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleAustralia

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