Crisaborole, a nonsteroidal phosphodiesterase 4 inhibitor, represents the first nonsteroidal medication approved for the treatment of atopic dermatitis in over a decade. In this work, crisaborole skin permeation and retention was studied in vitro from a 2% ointment using porcine skin as barrier. Crisaborole was also characterized in terms of thermal behavior, solubility, and logP. Control experiments were performed also on tape stripped skin to clarify the role of stratum corneum in drug partitioning and permeation across the skin. The results obtained indicate that crisaborole accumulates into the skin in considerable amounts after application of a topical lipophilic ointment. Crisaborole shows more affinity for the dermis compared to the epidermis despite its relatively high value of partition coefficient; stratum corneum analysis revealed a low affinity of the drug for this skin layer. Skin penetration across hair follicles or sebaceous glands can be a reason for the high dermis retention and is worth further investigation. The comparison with data obtained from a solution in acetonitrile suggests that the formulation plays a certain role in determining the relative distribution of crisaborole in the skin layers and in the receptor compartment.
Crisaborole is a boron compound recently approved by the US Food and Drug Administration as a 2% ointment for the treatment of mild to moderate atopic dermatitis. This work describes a simple method for the quantification of the drug in the skin layers at the end of in‐vitro permeation experiments. Chromatographic separation was carried out on a reverse‐phase C18 column using a mixture of trifluoroacetic acid 0.05%–acetonitrile (55:45, v/v) as mobile phase, pumped at 1 ml/min. Column temperature was 35°C and UV detection was performed at 250 nm. The method was linear in the range of concentration from 0.06 to 6 μg/ml (R2 = 1) and was selective, precise and accurate. Depending on the solvent used, the LOQ ranged from 0.014 to 0.030 μg/ml and the LOD from 0.005 to 0.010 μg/ml. The extraction from all the skin layers was quantitative. The developed method was successfully tested in an in‐vitro permeation study, proving to be an effective tool in the development of new formulations containing crisaborole.
Overexposure to sunlight is widely accepted as the underlying cause of cutaneous melanoma. UV radiation induces the formation of DNA photoproducts that, if unrepaired, can induce carcinogenic mutations. Recent data indicate that sorbates can be useful to widen the protection against UV radiation by acting as a triplet-state quencher in the melanocyte. The aim of the present work was to prepare an after sun formulation containing ethylsorbate or sorbic acid in order to take advantage of the triplet-state quenching activity of these molecules and protect the skin from UV-induced damages. Ethylsorbate and sorbic acid were characterized in terms of solubility and partition coefficient, and their transdermal permeation and skin accumulation were studied in vitro from simple solutions and in the presence of cyclodextrins (alpha and hydroxypropylbeta) as a complexing agent. The goal was to reduce as much as possible sorbates permeation while sustaining their skin levels. The obtained results indicated that the addition of alphacyclodextrins determined a 6-folds (ethylsorbate ) or 4-folds (sorbic acid) reduction of the transdermal permeation. Sorbic acid and alphacyclodextrin (1:1 molar ratio) were then formulated in an after sun vehicle using 1.5% hyaluronic acid (sodium salt) as a thickener and hydrating agent. The addition of hyaluronic acid gave rise to a formulation with good cosmetic properties and good sorbate (0.2–0.3 µmol/cm2) skin levels (stratum corneum + viable epidermis) and thus a potential protection against post-exposure UV damage.
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