Reduced Skin Permeation and Penetration of Clobetasol Propionate when Dermovate Cream is Applied at Short Time Intervals with Emollients

BackgroundDermovate cream containing 0.05% clobetasol propionate is a very potent topical corticosteroid (TCS) used in the treatment of severe inflammatory dermatoses. Regular emollient therapy should continue alongside clobetasol propionate treatment, however, the impact on drug delivery to the skin when both products are applied at similar times is unknown.ObjectivesTo assess whether application of emollients at similar times to Dermovate cream alter the delivery of clobetasol propionate to the skin.MethodsThis study was conducted using ex vivo human skin mounted in Franz cells. Dermovate cream was applied before or after three different emollients, Hydromol Intensive cream, Doublebase gel, and Diprobase ointment at 5- or 30-min intervals. Drug delivery to the skin was assessed up to 24 h using high-performance liquid chromatography.ResultsSignificantly reduced clobetasol propionate delivery to the skin was observed when Dermovate cream was applied either before or after the three different emollients, compared to the application of Dermovate cream alone. The data suggest in situ formation of a mixed Dermovate cream and emollient layer which reduces clobetasol propionate delivery relative to the original product. Applying Dermovate cream after any emollient generally resulted in larger reductions in drug delivery to the skin, compared to when the steroid was applied first. This was attributed to the emollients forming an additional barrier to drug delivery at the skin-formulation interface.ConclusionsThese findings indicate that applying Dermovate cream at similar times as emollients can significantly reduce drug delivery to the skin and that separating the application of the two products by intervals of up to 30 min is not sufficient to mitigate this effect. Depiction of Franz cell experiments and clinical application protocols of Dermovate cream with emollients, where the products are applied sequentially after 5 or 30 min. Hypothesised formulation effects on drug delivery are illustrated, showing a mixed Dermovate cream-emollient system on the skin surface and layering of the formulations causing barrier and occlusive effects. The clinical application protocols reducing drug delivery to human skin is shown, with larger decreases usually occurring when the emollient was applied before Dermovate cream. image