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.
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.
Authors: B Eberlein-König; T Schäfer; J Huss-Marp; U Darsow; M Möhrenschlager; O Herbert; D Abeck; U Krämer; H Behrendt; J Ring Journal: Acta Derm Venereol Date: 2000-05 Impact factor: 4.437
Authors: Dwayne T Friesen; Ravi Shanker; Marshall Crew; Daniel T Smithey; W J Curatolo; J A S Nightingale Journal: Mol Pharm Date: 2008 Nov-Dec Impact factor: 4.939