Skin permeation and penetration of crisaborole when coapplied with emollients

Draelos, Zoe Diana; Ports, William C.; Vlahos, Bonnie; Yeoh, Thean; Wu-Linhares, Dan; Brown, Marc; Lenn, J.; Thombre, Avinash G.

doi:10.1016/j.jaad.2020.03.114

Cited by 7 publications

(10 citation statements)

References 4 publications

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“…Applying Elocon cream after Diprobase cream or Diprobase ointment reduced MF delivery to the skin through reducing partitioning of the drug from the formulation into the skin. Similar findings have been reported from a recent study where crisaborole ointment applied up to 15 min after a commercially available cream or ointment significantly reduced drug permeation and penetration to the skin 11 . This behaviour was similar to that of the premixed Elocon cream and Diprobase cream and ointment systems, suggesting that formation of a physical emollient barrier layer by applying the emollient first does not explain the decreased MF delivery.…”

Section: Discussionsupporting

confidence: 88%

“…This is widely adopted by the pharmaceutical industry to understand the impact of an array of formulation factors on drug delivery to the skin, the demonstration of bioequivalence between formulations and can offer insight into the interplay occurring between emollients and TCSs in situ 10 . The approach has recently been used to provide data for post approval, medical affairs support on how to apply crisaborole ointment in relation to topical emollients 11 . In this work, the impact of altering the order of, and time interval between, applications of Elocon cream with three emollients on mometasone furoate (MF) delivery to ex vivo human skin was evaluated, alongside mechanistic investigations of changes in TCS absorption.…”

Section: Introductionmentioning

confidence: 99%

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Skin permeation and penetration of mometasone furoate in the presence of emollients: An ex vivo evaluation of clinical application protocols

Beebeejaun

Brown

Hutter

et al. 2023

Skin Health and Disease

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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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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Skin permeation and penetration of mometasone furoate in the presence of emollients: An ex vivo evaluation of clinical application protocols

Beebeejaun

Brown

Hutter

et al. 2023

Skin Health and Disease

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“…Barrier preparations are designed to help protect the skin from potential irritants and allergens, and so could conceivably impede drug uptake if applied first. A small-scale RCT appears to have found just this, with the application of emollient 15 min before TCS diminishing the response to the treatment compared with application of the emollient 15 min after the TCS (112,113). Current guidance for patients and healthcare professionals on the concomitant use of emollients and topical anti-inflammatory treatments is varied.…”

Section: The Interaction Between Vehicles and Other Topical Productsmentioning

confidence: 99%

Vehicles for atopic dermatitis therapies: more than just a placebo

Danby

Draelos

Gold

et al. 2020

Journal of Dermatological Treatment

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A topical vehicle is a 'carrier system' for an active pharmaceutical (or cosmetic) substance, referred to hereafter as the drug, but a vehicle may also be used on its own as an emollient to ameliorate dry skin. It is well established that the vehicle plays an important role in determining the bioavailability of a given drug at its ultimate target within the skin. Yet in the treatment of atopic eczema/dermatitis (AD), wherein the structure and function of the skin's outer barrier play a pivotal role in the development and course of the condition, the interaction of the vehicle with this barrier carries a particular importance. It is now clear that the often-considered inert excipients of a vehicle bring about changes within the skin at the molecular level that promote barrier restoration and enhance innate immune defenses with therapeutic value to AD patients. Moreover, the vehicle control in randomized controlled trials (RCTs) increasingly displays significant efficacy. In light of this, we consider the implications of vehicle design in relation to AD pathophysiology and the role vehicles play as controls in RCTs of new drug treatments for this condition.

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“…Previous work has demonstrated that in situ mixing of a saturated TCS formulation with different emollients resulted in a range of complex formulation changes which increased or decreased drug delivery to the skin to varying extents 6 . Applying crisaborole ointment 15 min before an emollient was found to prevent the decreased absorption observed when the crisaborole ointment was applied after an emollient 12 . In this study, administration of Dermovate cream with Diprobase ointment, Doublebase gel, or Hydromol Intensive cream in situ across 5‐ or 30‐min intervals or before application invariably reduced clobetasol propionate delivery to the skin.…”

Section: Resultsmentioning

confidence: 98%

“…This approach is widely used by the pharmaceutical industry to understand the impact of formulation composition on drug delivery to the skin or to evaluate bioequivalence between formulations and it can provide insight into the effect of emollients on clobetasol propionate absorption from Dermovate cream 11 . It has also been used to inform medical affairs answers to post approval questions on how to apply emollients when patients are being treated with the nonsteroidal phosphodiesterase 4 inhibitor, crisaborole 12 . Three marketed emollient products, Diprobase ointment, Doublebase gel, and Hydromol Intensive cream, which have different compositions were selected to provide an indication of the effects different types of emollients may have when applied to the skin at short time intervals (≤30 min) with Dermovate cream.…”

Section: Introductionmentioning

confidence: 99%

Reduced skin permeation and penetration of clobetasol propionate when Dermovate cream is applied at short time intervals with emollients

Beebeejaun

Brown

Hutter

et al. 2023

JEADV Clinical Practice

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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.

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Skin permeation and penetration of crisaborole when coapplied with emollients

Cited by 7 publications

References 4 publications

Skin permeation and penetration of mometasone furoate in the presence of emollients: An ex vivo evaluation of clinical application protocols

Skin permeation and penetration of mometasone furoate in the presence of emollients: An ex vivo evaluation of clinical application protocols

Vehicles for atopic dermatitis therapies: more than just a placebo

Reduced skin permeation and penetration of clobetasol propionate when Dermovate cream is applied at short time intervals with emollients

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