Yang Yang, Ako-Adounvo Ann-Marie, Wang Jiang, Coelho Sergio G, Adah Steven A, Matta Murali K, Strauss David, Michele Theresa M, Wang Jian, Faustino Patrick J, O'Connor Thomas, Ashraf Muhammad
Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, FDA, 10903 New Hampshire Avenue, WO64-Rm1032, Silver Spring, Maryland, 20993, USA.
Office of Nonprescription Drugs, Office of New Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA.
AAPS PharmSciTech. 2022 Apr 22;23(5):121. doi: 10.1208/s12249-022-02275-z.
Evaluating the dermal absorption of sunscreen UV filters requires the development of a bio-predictable in vitro permeation test (IVPT). This work describes the comparison of two IVPT methods and rank order correlations of in vitro absorption (skin permeation and retention) with the in vivo absorption (AUC and skin retention) of sunscreens. The IVPT was compared regarding the following elements: (1) application of a single finite dose vs. an infinite dose and (2) the use of heat-separated human epidermis vs. dermatomed skin models. The IVPT was used to evaluate dermal absorption of six UV filters (avobenzone, homosalate, octinoxate, octisalate, octocrylene, and oxybenzone) in commercial sunscreens. Both the in vivo and in vitro permeation studies demonstrated that all UV filters were absorbed following a single-dose application. Sunscreens were rank ordered by the amount of the UV filters absorbed. Data obtained from the IVPT method using a single finite dose and heat-separated human epidermis was found to correlate with the clinical data. Rank orders of the cumulative in vitro skin permeation and the in vivo AUC were found comparable for oxybenzone, homosalate, octisalate, and octinoxate. Rank orders of the in vitro and in vivo skin retention of oxybenzone and octinoxate were also comparable. Additional IVPT parameters may be optimized to enhance the discriminatory power for UV filters with low skin permeation potential (e.g., avobenzone and octocrylene).
评估防晒紫外线过滤剂的皮肤吸收需要开发一种具有生物可预测性的体外渗透试验(IVPT)。这项工作描述了两种IVPT方法的比较,以及防晒剂体外吸收(皮肤渗透和滞留)与体内吸收(AUC和皮肤滞留)的排序相关性。对IVPT在以下方面进行了比较:(1)单次有限剂量与无限剂量的应用,以及(2)热分离人表皮与皮片皮肤模型的使用。IVPT用于评估市售防晒剂中六种紫外线过滤剂(阿伏苯宗、胡莫柳酯、桂皮酸盐、水杨酸辛酯、奥克立林和二苯甲酰甲烷)的皮肤吸收。体内和体外渗透研究均表明,单次给药后所有紫外线过滤剂均被吸收。根据紫外线过滤剂的吸收量对防晒剂进行排序。发现使用单次有限剂量和热分离人表皮的IVPT方法获得的数据与临床数据相关。对于二苯甲酰甲烷、胡莫柳酯、水杨酸辛酯和桂皮酸盐,体外皮肤累积渗透和体内AUC的排序具有可比性。二苯甲酰甲烷和桂皮酸盐的体外和体内皮肤滞留排序也具有可比性。可以优化其他IVPT参数,以提高对皮肤渗透潜力低的紫外线过滤剂(如阿伏苯宗和奥克立林)的区分能力。