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

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

KEY WORDS

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

Abbreviations

4-BPB

4-bromophenylboronic acid

AUC

Area under the curve

GI

Gastrointestinal

HPLC

High performance liquid chromatography

LBF

Lipid-based formulation

LFCS

Lipid Formulation Classification System

NaTDC

Sodium taurodeoxycholate

PC

Phosphatidylcholine

TBU

Tributyrin units

UPLCMS/MS

Ultra performance liquid chromatography – tandem mass spectrometer

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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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