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用于治疗痤疮的壬二酸局部递送的深共晶溶剂的配方和评价。

The Formulation and Evaluation of Deep Eutectic Vehicles for the Topical Delivery of Azelaic Acid for Acne Treatment.

机构信息

Faculty of Pharmacy, Pharmacological and Diagnostic Research Center, Al-Ahliyya Amman University, Amman 19328, Jordan.

Department of Pharmaceutics, College of Pharmacy, University of Sulaimani, Sulaimani 46001, Kurdistan Region, Iraq.

出版信息

Molecules. 2023 Oct 4;28(19):6927. doi: 10.3390/molecules28196927.

Abstract

The current work was aimed at the development of a topical drug delivery system for azelaic acid (AzA) for acne treatment. The systems tested for this purpose were deep eutectic systems (DESs) prepared from choline chloride (CC), malonic acid (MA), and PEG 400. Three CC to MA and eight different MA: CC: PEG400 ratios were tested. The physical appearance of the tested formulations ranged from solid and liquid to semisolid. Only those that showed liquid formulations of suitable viscosity were considered for further investigations. A eutectic mixture made from MA: CC: PEG400 1:1:6 (MCP 116) showed the best characteristics in terms of viscosity, contact angle, spreadability, partition coefficient, and in vitro diffusion. Moreover, the MCP116 showed close rheological properties to the commercially available market lead acne treatment product (Skinorin). In addition, the formula showed synergistic antibacterial activity between the MA moiety of the DES and the AzA. In vitro diffusion studies using polyamide membranes demonstrated superior diffusion of MCP116 over the pure drug and the commercial product. No signs of skin irritation and edema were observed when MCP116 was applied to rabbit skin. Additionally, the MCP116 was found to be, physically and chemically, highly stable at 4, 25, and 40 °C for a one-month stability study.

摘要

本研究旨在开发一种用于治疗痤疮的壬二酸(AzA)局部给药系统。为此目的测试了深共晶溶剂(DES),由氯化胆碱(CC)、丙二酸(MA)和 PEG400 制备。测试了三种 CC 与 MA 以及八种不同 MA:CC:PEG400 比例的 DES。测试配方的物理外观从固体和液体到半固体。只有那些显示出合适粘度的液体配方才被认为是进一步研究的对象。由 MA:CC:PEG400 1:1:6(MCP116)组成的共晶混合物在粘度、接触角、铺展性、分配系数和体外扩散方面表现出最佳特性。此外,MCP116 表现出与市售痤疮治疗产品(Skinorin)相近的流变学特性。此外,该配方显示出 DES 的 MA 部分与 AzA 之间的协同抗菌活性。使用聚酰胺膜进行的体外扩散研究表明,MCP116 的扩散性能优于纯药物和商业产品。当 MCP116 应用于兔皮时,没有观察到皮肤刺激和水肿的迹象。此外,经过一个月的稳定性研究,MCP116 在 4、25 和 40°C 下表现出物理和化学上的高度稳定性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0bd/10574101/10ff66f626f3/molecules-28-06927-g001.jpg

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