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The Asymmetry of the Unstirred Water Layer in Permeability Experiments

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Abstract

Purpose

To elucidate the apical and basolateral components of the total unstirred water layer in regular permeability experiment.

Methods

A novel stirring apparatus was constructed to remove the basolateral unstirred water layer. Caco-2 cells were used as the permeability barrier both in Transwell-type and side-by-side apparatuses. Permeability experiments were done with several ionisable compounds at various pH and stirring conditions. The permeabilities of the cell monolayer, the unstirred water layer and the polycarbonate filter were calculated either from experimental data or theoretically.

Results

The unstirred water layer was thicker in the Transwell apparatus than in the side-by-side chamber even in the presence of vigorous basolateral magnetic stirring. Calculations indicated that the apical unstirred water layer is thicker than the basolateral layer. Different cellular permeability coefficients were obtained from the two permeability apparatuses.

Conclusions

An orbital shaker does not produce symmetric hydrodynamics in both chambers of Transwell apparatus. The asymmetric unstirred water layer may complicate the exact analysis of polarized transport.

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Abbreviations

AB:

apical-to-basolateral

AB Stir:

apical-to-basolateral with basolateral magnetic stirring

BA:

basolateral-to-apical

BA Stir:

basolateral-to-apical with basolateral magnetic stirring

SbS:

side-by-side chamber

TW:

TransWell apparatus

UWL:

unstirred water layer

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Acknowledgements

This study was financially supported by the Finnish Foundation for Technology and Innovation, The Finnish Cultural Foundation of Northern-Savo, Emil Aaltonen Foundation, The Association of Finnish Pharmacies and The Finnish Pharmaceutical Society. The skillful technical assistance from Mr. Markku Taskinen is gratefully acknowledged. The authors wish to thank Ewen MacDonald, Ph.D., for revising the language of the manuscript.

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Authors and Affiliations

  1. Department of Pharmaceutics, University of Kuopio, P.O. Box 1627, 70211, Kuopio, Finland

    Timo Korjamo, Aki T. Heikkinen & Jukka Mönkkönen

  2. ABB Ltd., Helsinki, Finland

    Pekka Waltari

Authors
  1. Timo Korjamo
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  2. Aki T. Heikkinen
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  3. Pekka Waltari
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  4. Jukka Mönkkönen
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Correspondence to Timo Korjamo.

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Korjamo, T., Heikkinen, A.T., Waltari, P. et al. The Asymmetry of the Unstirred Water Layer in Permeability Experiments. Pharm Res 25, 1714–1722 (2008). https://doi.org/10.1007/s11095-008-9573-8

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  • DOI: https://doi.org/10.1007/s11095-008-9573-8

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