Development, Characterization, and Ex Vivo Permeation Assessment of Diclofenac Diethylamine Deep Eutectic Systems Across Human Skin

Abstract

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.

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Al-Mawla, L., Al-Akayleh, F., Daadoue, S. et al. Development, Characterization, and Ex Vivo Permeation Assessment of Diclofenac Diethylamine Deep Eutectic Systems Across Human Skin. J Pharm Innov (2023). https://doi.org/10.1007/s12247-023-09784-9

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