caa a22 4500 445313021 CHVBK 20180317142636.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s11095-011-0488-4 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0488-4 Using pH Abnormalities in Diseased Skin to Trigger and Target Topical Therapy [Elektronische Daten] [Khalida Rizi, Rebecca Green, Michael Donaldson, Adrian Williams] 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. Springer Science+Business Media, LLC, 2011 Carbopol nationallicence Eudragit L100 nationallicence hydrocortisone nationallicence hydroxypropyl methyl cellulose nationallicence pH-responsive microparticles nationallicence Rizi Khalida Reading School of Pharmacy, University of Reading, Whiteknights, P.O. Box226, RG6 6AP, Reading, UK aut Green Rebecca Reading School of Pharmacy, University of Reading, Whiteknights, P.O. Box226, RG6 6AP, Reading, UK aut Donaldson Michael Stiefel Laboratories, Eurasia Headquarters, Concorde Road, SL6 4BY, Maidenhead, UK aut Williams Adrian Reading School of Pharmacy, University of Reading, Whiteknights, P.O. Box226, RG6 6AP, Reading, UK aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/10(2011-10-01), 2589-2598 0724-8741 28:10<2589 2011 28 11095 https://doi.org/10.1007/s11095-011-0488-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0488-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rizi Khalida Reading School of Pharmacy, University of Reading, Whiteknights, P.O. Box226, RG6 6AP, Reading, UK aut NATIONALLICENCE 700 1- Green Rebecca Reading School of Pharmacy, University of Reading, Whiteknights, P.O. Box226, RG6 6AP, Reading, UK aut NATIONALLICENCE 700 1- Donaldson Michael Stiefel Laboratories, Eurasia Headquarters, Concorde Road, SL6 4BY, Maidenhead, UK aut NATIONALLICENCE 700 1- Williams Adrian Reading School of Pharmacy, University of Reading, Whiteknights, P.O. Box226, RG6 6AP, Reading, UK aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/10(2011-10-01), 2589-2598 0724-8741 28:10<2589 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer