Pharmaceutical Research

, Volume 30, Issue 12, pp 3045–3058 | Cite as

Lipid Absorption Triggers Drug Supersaturation at the Intestinal Unstirred Water Layer and Promotes Drug Absorption from Mixed Micelles

  • Yan Yan Yeap
  • Natalie L. Trevaskis
  • Christopher J. H. Porter
Research Paper



To evaluate the potential for the acidic intestinal unstirred water layer (UWL) to induce drug supersaturation and enhance drug absorption from intestinal mixed micelles, via the promotion of fatty acid absorption.


Using a single-pass rat jejunal perfusion model, the absorptive-flux of cinnarizine and 3H-oleic acid from oleic acid-containing intestinal mixed micelles was assessed under normal acidic microclimate conditions and conditions where the acidic microclimate was attenuated via the co-administration of amiloride. As a control, the absorptive-flux of cinnarizine from micelles of Brij® 97 (a non-ionizable, non-absorbable surfactant) was assessed in the absence and presence of amiloride. Cinnarizine solubility was evaluated under conditions of decreasing pH and decreasing micellar lipid content to assess likely changes in solubilization and thermodynamic activity during micellar passage across the UWL.


In the presence of amiloride, the absorptive-flux of cinnarizine and 3H-oleic acid from mixed micelles decreased 6.5-fold and 3.0-fold, respectively. In contrast, the absorptive-flux of cinnarizine from Brij® 97 micelles remained unchanged by amiloride, and was significantly lower than from the long-chain micelles. Cinnarizine solubility in long-chain micelles decreased under conditions where pH and micellar lipid content decreased simultaneously.


The acidic microclimate of the intestinal UWL promotes drug absorption from intestinal mixed micelles via the promotion of fatty acid absorption which subsequently stimulates drug supersaturation. The observations suggest that formulations (or food) containing absorbable lipids (or their digestive precursors) may outperform formulations that lack absorbable components since the latter do not benefit from lipid absorption-induced drug supersaturation.

Key words

absorption food effect lipid based formulations poorly water soluble drug supersaturation unstirred water layer 



Cluster of Differentiation 36




fatty acid transport protein




high performance liquid chromatography


Lipid based formulation


long-chain fatty acid


Lipid Formulation Classification System




oleic acid


poorly water-soluble drugs


simulated endogenous intestinal fluid


Scavenger Receptor Class B Type I


unstirred water layer


Acknowledgments and Disclosures

Funding support from the National Health and Medical Research Council (NHMRC) of Australia is gratefully acknowledged.

Supplementary material

11095_2013_1104_MOESM1_ESM.docx (3.1 mb)
ESM 1 (DOCX 3.14 mb)


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Drug Delivery, Disposition and Dynamics Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleAustralia

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