Purpose

The primary aim of this study is to introduce Therapeutic Deep Eutectic Systems (THEDES) as a novel, green, and biocompatible solvent system for the delivery of diclofenac diethylamine (DDEA), a non-steroidal anti-inflammatory drug. The research question focuses on whether THEDES could significantly enhance the solubility and release kinetics of DDEA compared to conventional solvents.

Methods

The THEDES formulation comprises capric acid, menthol, and Gelucire® 33/01 in varying ratios. Techniques such as Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), rheology measurement, and contact angle tests were employed to characterize and investigate the drug solubilization process. Ex vivo permeation studies using Franz diffusion cells and human skin were conducted to assess drug release kinetics.

Results

The developed THEDES demonstrated unique molecular interactions and interfacial properties, with glass transition temperatures below − 50 °C and a broad spectrum of endothermic melting points, indicating excellent phase stability. The solubility of DDEA in THEDES was approximately 101 mg/ml, which is a tenfold and threefold increase compared to solvents like dimethyl sulfoxide and ethanol, respectively. Enhanced drug release kinetics were observed when compared with Voltaren® Emulgel, a commercial formulation. Histopathological evaluations indicated no signs of skin erythema, inflammation, or erosion, confirming the biocompatibility of the formulation.

Conclusion

THEDES emerges as a potent, green, biocompatible solvent system for efficiently delivering DDEA. It exhibits superior solubilization capacities and favorable release kinetics, coupled with high biocompatibility, offering significant advantages over traditional solvent systems for drug delivery applications.

Graphical Abstract

中文翻译：

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双氯芬酸二乙胺深层共晶系统在人体皮肤中的开发、表征和离体渗透评估

目的

本研究的主要目的是介绍治疗性深层共晶系统 (THEDES) 作为一种新型、绿色、生物相容性溶剂系统，用于输送双氯芬酸二乙胺 (DDEA)（一种非甾体抗炎药）。研究问题集中于与传统溶剂相比，THEDES 是否可以显着提高 DDEA 的溶解度和释放动力学。

方法

THEDES 配方包含不同比例的癸酸、薄荷醇和 Gelucire® 33/01。采用傅里叶变换红外光谱（FTIR）、差示扫描量热法（DSC）、流变测量和接触角测试等技术来表征和研究药物溶解过程。使用 Franz 扩散池和人体皮肤进行离体渗透研究，以评估药物释放动力学。

结果

开发的 THEDES 表现出独特的分子相互作用和界面特性，玻璃化转变温度低于 − 50 °C，吸热熔点范围广，表明具有出色的相稳定性。DDEA 在 THEDES 中的溶解度约为 101 mg/ml，与二甲亚砜和乙醇等溶剂相比，分别增加了 10 倍和 3 倍。与商用制剂 Voltaren® Emulgel 相比，观察到药物释放动力学增强。组织病理学评估表明没有皮肤红斑、炎症或糜烂的迹象，证实了该制剂的生物相容性。

结论

THEDES 是一种有效、绿色、生物相容的溶剂系统，可有效输送 DDEA。它具有卓越的增溶能力和良好的释放动力学，再加上高生物相容性，在药物输送应用中比传统溶剂系统具有显着优势。

图形概要