LEO Foundation Center for Cutaneous Drug Delivery, Department of Pharmacy, University of Copenhagen, 2100 Copenhagen, Denmark.
LEO Foundation Center for Cutaneous Drug Delivery, Department of Pharmacy, University of Copenhagen, 2100 Copenhagen, Denmark.
Int J Pharm. 2024 Oct 25;664:124615. doi: 10.1016/j.ijpharm.2024.124615. Epub 2024 Aug 20.
Terpene-based eutectic mixtures (EMs) are attractive platforms for transdermal delivery due to their solubilizing potential and ability to alter the barrier function of the stratum corneum (SC). Despite this, little is known about the effect of diluting EMs with co-solvents (CSs) on their solubility- and permeation-enhancing properties. Furthermore, insufficient attention has been paid to comparing these platforms with traditional solvents, such as propylene glycol (PG) or ethanol (EtOH). To address this gap, the present study investigates the impact of the CS content in EM:CS blends on the transdermal delivery of clotrimazole (CLOT). Two CSs, PG and EtOH, and two terpene-based EMs, menthol:thymol and thymol:β-citronellol, were used. Each of the EMs was investigated at two different molar ratios between the terpenes, with one being their eutectic point, to explore its potential benefit for skin permeation. At each step, properties of the blends were compared with those of pure CSs. The EM:CS blends showed a better solubilizing potential for CLOT than EMs or CSs on their own. A higher content of CSs in the blends resulted in a higher skin permeation and retention of CLOT, and a lower degree of disarrangement of the SC structure. Furthermore, the blends of EMs at their EPs led to overall poorer permeation profiles, implying that the permeation rate is more affected by the properties of the individual terpenes than by the specific ratio at the eutectic point between them. In conclusion, addition of CSs to the EMs promotes permeation and retention of CLOT, while reducing the skin impairment caused by the terpenes.
基于萜烯的共晶混合物（EMs）由于其增溶潜力和改变角质层（SC）屏障功能的能力，是透皮递送的有吸引力的平台。尽管如此，对于用共溶剂（CSs）稀释 EMs 对其增溶和渗透增强特性的影响知之甚少。此外，对于将这些平台与传统溶剂（如丙二醇（PG）或乙醇（EtOH））进行比较，关注不够。为了解决这一差距，本研究调查了 CS 含量在 EM:CS 混合物中对克霉唑（CLOT）透皮递送的影响。使用了两种 CS，PG 和 EtOH，以及两种基于萜烯的 EMs，薄荷醇：百里酚和百里酚：β-香茅醇。每种 EM 都在萜烯之间的两个不同摩尔比下进行了研究，其中一个是共晶点，以探索其对皮肤渗透的潜在益处。在每个步骤中，都将混合物的性质与纯 CSs 的性质进行了比较。与单独的 EM 或 CS 相比，EM:CS 混合物对 CLOT 的增溶潜力更好。混合物中 CSs 的含量越高，CLOT 的皮肤渗透和保留越高，SC 结构的无序程度越低。此外，EM 混合物在其共晶点的混合物导致整体较差的渗透曲线，这意味着渗透速率受单个萜烯的性质影响大于它们之间共晶点的特定比例的影响。总之，向 EMs 添加 CSs 可促进 CLOT 的渗透和保留，同时减少萜烯对皮肤的损伤。
