Background: Topical corticosteroids (TCS) and emollients are developed independently by the pharmaceutical industry but are often used together in practice. There is potential for the TCS and emollient formulations to interact on the skin surface affecting TCS absorption into the skin. Clinical guidelines acknowledge this issue but lack an evidence base and differ in their recommendations. There is a current clinical need to establish whether the application protocol employed for TCS and emollient products can impact delivery of TCS to the skin. Objectives: To investigate whether the sequence of application of a TCS and emollient and the time between their application can affect TCS skin absorption. Methods: The delivery of mometasone furoate (MF) to ex vivo human skin was evaluated following the application of Elocon cream either 5 or 30 min, before and after three different emollients. Mechanistic explanation of the changes in drug absorption was provided by modelling the skin permeation data and Raman microscopy of mixed Elocon cream and emollient formulations. Results: A circa fivefold difference in MF absorption was observed depending on the emollient and application protocol. Applying Elocon cream at short intervals in relation to Hydromol intensive significantly increased MF absorption regardless of the application protocol. In contrast, applying Elocon cream after Diprobase cream or ointment significantly reduced MF absorption relative to Elocon cream alone or when Elocon cream was applied before these emollients. The changes in drug absorption observed were attributed to the presence of emollients altering Elocon cream formulation performance through different mechanisms, including introduction of penetration enhancing excipients and inducing drug crystallization in the mixed TCS emollient layer on the skin surface. Conclusions: Emollients can affect MF absorption in different ways depending on the emollient and sequence of administration. Using a 30 min gap between product applications may not be sufficient to mitigate emollient effects on TCS absorption.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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This work investigated the permeability of lidocaine across human eyelid skin and compared this with published data for abdominal skin to understand the characteristics of this type of skin and whether topical anaesthesia for eyelid surgery may be feasible. Eyelid skin is thought to have a relatively high permeability to drugs, however how this compares to other body sites has not been previously quantified. Lidocaine solutions at pH 7.0 and 5.5 were applied to human eyelid skin mounted in Franz diffusion cells. Anatomical features of eyelid skin that may be linked to its increased permeability, superficial corneocyte area and stratum corneum (SC) thickness were measured using light microscopy. Steady-state fluxes of lidocaine at pH 7.0 and pH 5.5 were 283.9 and 41.0 µg/cm 2 /hr, 2.4 and 3.2 times greater respectively than literature values for abdominal skin. Superficial eyelid corneocyte area (800.5 µm 2) was 35% smaller and the eyelid SC thickness (14.9 µm) was 31% thinner than reported abdominal skin values. These suggest that a shorter diffusional pathlength across the eyelid SC contributes to increased lidocaine permeability. The relatively high permeability of eyelid skin to lidocaine indicates considerable potential for achieving strong topical anaesthetic effects at this site.

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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.