Rost Daiane L, Barbalho Geisa N, Andrade Jayanaraian F M, Cunha-Filho Marcilio, Gelfuso Guilherme M, Gratieri Tais
Laboratory of Food, Drugs, and Cosmetics (LTMAC), University of Brasilia (UnB), Brasília 70910-900, DF, Brazil.
Pharmaceutics. 2025 Jul 3;17(7):874. doi: 10.3390/pharmaceutics17070874.
The treatment of atopic dermatitis frequently involves using a topical corticosteroid and a moisturizer. While the sequential application of these products is a common dermatological practice, their influence on drug penetration remains poorly understood. There is no clear evidence on how hydration, application sequence, and massage affect cutaneous drug delivery. Hence, this study aimed to evaluate the effects of formulation type, moisturizer composition, application sequence, and mechanical stimulation on betamethasone dipropionate (BET) cutaneous penetration. Two commercial formulations (cream and ointment) of BET were evaluated in different experimental conditions, including drug application combined with moisturizers (Cetaphil, as an emollient; Nivea, as an occlusive) pre- or post-application, with or without a 30 s massage. In vitro skin penetration assays were conducted for 12 h using porcine skin mounted in modified Franz diffusion cells. BET levels were extracted from the skin layers and quantified by HPLC. The cutaneous BET penetration was strongly influenced by the application sequence, type of moisturizer, and mechanical stimuli. Pre-application of an occlusive or emollient moisturizer, followed by 30 s physical stimuli, significantly enhanced drug retention in the stratum corneum. For the cream, pre-application of moisturizers followed by massage notably increased BET levels in both the stratum corneum and viable skin. Conversely, post-application of moisturizers hindered BET absorption. The ointment showed limited penetration across all conditions, with no drug detected in the viable skin. The results showed pre-hydrating the skin, combined with a 30 s massage, was the best strategy for BET diffusion into the skin following cream administration. The formulation type and the order of application directly influence the effectiveness of drug therapy and the topical absorption of BET.
特应性皮炎的治疗通常涉及使用外用皮质类固醇和保湿剂。虽然依次使用这些产品是常见的皮肤科做法，但它们对药物渗透的影响仍知之甚少。关于水合作用、涂抹顺序和按摩如何影响皮肤给药，尚无明确证据。因此，本研究旨在评估剂型、保湿剂成分、涂抹顺序和机械刺激对丙酸倍他米松（BET）皮肤渗透的影响。在不同实验条件下评估了两种BET商业制剂（乳膏和软膏），包括在涂抹药物之前或之后联合使用保湿剂（丝塔芙，作为润肤剂；妮维雅，作为封闭剂），有无30秒的按摩。使用安装在改良弗兰兹扩散池中的猪皮进行了12小时的体外皮肤渗透试验。从皮肤层中提取BET水平，并通过高效液相色谱法进行定量。皮肤BET渗透受到涂抹顺序、保湿剂类型和机械刺激的强烈影响。在涂抹封闭剂或润肤剂保湿剂后进行30秒的物理刺激，可显著提高药物在角质层中的保留率。对于乳膏，先涂抹保湿剂然后按摩，显著提高了角质层和活皮肤中的BET水平。相反，在涂抹药物后使用保湿剂会阻碍BET的吸收。在所有条件下，软膏的渗透都有限，在活皮肤中未检测到药物。结果表明，在涂抹乳膏后，预先给皮肤补水并结合30秒的按摩，是BET扩散到皮肤中的最佳策略。剂型和涂抹顺序直接影响药物治疗的有效性和BET的局部吸收。
