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Table of Contents
Vol. 14, Suppl. 1, 2001
Issue release date: August 2001

Modulation of the Barrier Function of the Skin

Hadgraft J.
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Abstract

Transport of xenobiotics across the stratum corneum, the rate-controlling membrane of skin, is slow and the mechanism appears complex. However, the basic transfer is controlled by fundamental physicochemical concepts, the predominant of which are partition (K), diffusion (D) and solubility (Cs). In order to change the rate of penetration it is therefore clear that it is these parameters that should be targeted. In most instances enhancement strategies are adopted to improve D, K or Cs, however there are instances in which permeation reduction may be beneficial. Examples include the topical application of sunscreens or insect repellents. This publication demonstrates the way in which modulation effects can be assessed and the difficulties involved in determining which of the physicochemical parameter(s) are being affected. If the formulation influences more than one, synergism can often be seen. Advances in computer modelling have provided an insight into the mechanisms of action of some of the chemical enhancers at a molecular level. Enhanced skin absorption has been reported for the delivery of macromolecules such as insulin (associated with transfersomes) or DNA (as a DOTAP complex). The barrier property of the skin must be modulated for this to be achieved. However the precise mechanisms of action have not been elucidated.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

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    External Resources

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  4. Mitragotri S: In situ determination of partition and diffusion coefficients in the lipid bilayers of stratum corneum. Pharm Res 2000;17:1026–1029.

    External Resources

  5. Pellett MA, Watkinson AC, Hadgraft J, Brain KR: Comparison of permeability data from traditional diffusion cells and ATR-FTIR spectroscopy. 1. Synthetic membranes. Int J Pharm 1997;154:205–215.
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    External Resources

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  17. Iervolino M, Cappello B, Raghavan SL, Hadgraft, J: Penetration enhancement of ibuprofen from supersaturated solutions through human skin. Int J Pharm 2001;212:131–141.

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  18. Hadgraft J, Valenta C: pH, pK(a) and dermal delivery. Int J Pharm 2000;200:243–247.
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    External Resources

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