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.

中文翻译：

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Crisaborole 局部应用后的体外皮肤保留。

Crisaborole 是一种非甾体磷酸二酯酶 4 抑制剂，是十多年来第一种被批准用于治疗特应性皮炎的非甾体药物。在这项工作中，使用猪皮肤作为屏障，在体外研究了 2% 软膏中 Crisaborole 的皮肤渗透和保留情况。Crisaborole 还根据热行为、溶解度和 logP 进行了表征。还在胶带剥离的皮肤上进行了对照实验，以阐明角质层在药物分配和跨皮肤渗透中的作用。获得的结果表明，在使用局部亲脂性软膏后，crisaborole 会大量积聚到皮肤中。尽管 Crisaborole 的分配系数值相对较高，但与表皮相比，Crisaborole 对真皮的亲和力更强；角质层分析显示该药物对该皮肤层的亲和力较低。皮肤渗透毛囊或皮脂腺可能是真皮保留率高的原因，值得进一步研究。与乙腈溶液中获得的数据的比较表明，该制剂在确定crisaborole在皮肤层和受体室中的相对分布方面发挥一定作用。