Novel therapeutic deep eutectic system for the enhancement of ketoconazole antifungal activity and transdermal permeability

In this study, we reported the investigation of a novel therapeutic deep eutectic system (THEDES) formed between capric acid (CA) and ketoconazole (KCZ) to enhance the permeability and efficacy of the antifungal drug KCZ. A THEDES was formulated by combining KCZ and CA at different molar ratios, with a 1:5 ratio (K5) representing the most stable and lowest melting point. Characterization of the interactions between CA and KCZ using NMR and FT-IR spectroscopy revealed a hydrogen bonding interaction between the amine group of KCZ's imidazole ring and the carboxylic acid moiety of CA. This interaction resulted in converting the solid materials into liquid at room temperature, leading to a significant decrease in the melting points of the components, as confirmed by DSC. Next, the effectiveness of K5 as an antifungal agent against Candida albicans was evaluated. The results indicated a 2-fold reduction in the minimum inhibitory concentration (MIC). In addition, permeability studies conducted using a Franz diffusion cell revealed a significant enhancement in permeability with a 6.19-fold increase in flux compared to commercially available KCZ cream. The findings suggest that fatty acid-based deep eutectic systems, such as the KCZ THEDES, can serve as effective and green drug delivery systems, offering significant enhancements in drug permeability and therapeutic performance. This approach improves the efficacy of drugs and promotes the development of eco-friendly pharmaceutical formulations.