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Using pH Abnormalities in Diseased Skin to Trigger and Target Topical Therapy

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ABSTRACT

Purpose

The pH discrepancy between healthy and atopic dermatitis skin was identified as a site-specific trigger for delivering hydrocortisone from microcapsules.

Methods

Using Eudragit L100, a pH-responsive polymer which dissolves at pH 6, hydrocortisone-loaded microparticles were produced by oil-in-oil microencapsulation or spray drying. Release and permeation of hydrocortisone from microparticles alone or in gels was assessed, and preliminary stability data was determined.

Results

Drug release from microparticles was pH-dependent, though the particles produced by spray drying also gave significant non-pH-dependent burst release, resulting from their porous nature or from drug enrichment on the surface of these particles. This pH-responsive release was maintained upon incorporation of the oil-in-oil microparticles into Carbopol- and HPMC-based gel formulations. In vitro studies showed 4- to 5-fold higher drug permeation through porcine skin from the gels at pH 7 compared to pH 5.

Conclusions

Permeation studies showed that the oil-in-oil-generated particles deliver essentially no drug at normal (intact) skin pH (5.0–5.5) but that delivery can be triggered and targeted to atopic dermatitis skin where the pH is elevated. The incorporation of these microparticles into Carbopol- and HPMC-based aqueous gel formulations demonstrated good stability and pH-responsive permeation into porcine skin.

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ACKNOWLEDGMENTS & DISCLOSURES

The authors thank Stiefel laboratories Ltd., a GSK company, for their financial support.

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Authors and Affiliations

  1. Reading School of Pharmacy, University of Reading, Whiteknights, P.O. Box 226, Reading, RG6 6AP, UK

    Khalida Rizi, Rebecca J. Green & Adrian C. Williams

  2. Stiefel Laboratories, Eurasia Headquarters, Concorde Road, Maidenhead, SL6 4BY, UK

    Michael X. Donaldson

Authors
  1. Khalida Rizi
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  2. Rebecca J. Green
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  3. Michael X. Donaldson
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  4. Adrian C. Williams
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Corresponding author

Correspondence to Adrian C. Williams.

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Rizi, K., Green, R.J., Donaldson, M.X. et al. Using pH Abnormalities in Diseased Skin to Trigger and Target Topical Therapy. Pharm Res 28, 2589–2598 (2011). https://doi.org/10.1007/s11095-011-0488-4

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  • DOI: https://doi.org/10.1007/s11095-011-0488-4

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