Fantini Adriana, Demurtas Anna, Nicoli Sara, Padula Cristina, Pescina Silvia, Santi Patrizia
Department of Food and Drug, University of Parma, Parco Area delle Scienze 27/a, 43124 Parma, Italy.
Pharmaceutics. 2020 May 28;12(6):491. doi: 10.3390/pharmaceutics12060491.
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.
克立硼罗是一种非甾体类磷酸二酯酶4抑制剂，是十多年来首个被批准用于治疗特应性皮炎的非甾体类药物。在这项研究中，以猪皮为屏障，对2%克立硼罗软膏的体外皮肤渗透和滞留情况进行了研究。还对克立硼罗的热行为、溶解度和logP进行了表征。同时也对胶带剥离皮肤进行了对照实验，以阐明角质层在药物在皮肤中的分配和渗透中的作用。所得结果表明，局部应用亲脂性软膏后，克立硼罗会大量积聚在皮肤中。尽管克立硼罗的分配系数相对较高，但与表皮相比，它对真皮表现出更高的亲和力；角质层分析表明该药物对这一皮肤层的亲和力较低。药物通过毛囊或皮脂腺穿透皮肤可能是其在真皮中高滞留率的一个原因，值得进一步研究。与从乙腈溶液中获得的数据相比表明，制剂在决定克立硼罗在皮肤各层和受体室中的相对分布方面发挥了一定作用。
