Can deep eutectic mixtures affect the skin permeation and rheological behavior of thermoresponsive hydrogels? A case study with ibuprofen

Ibuprofen (IBU) is widely used for the topical treatment of inflammatory disorders; however, its tendency to crystallize in aqueous vehicles and limited cutaneous permeation pose significant formulation challenges. Then, the formation of an ibuprofen-menthol deep eutectic mixture (EM) and subsequent incorporation into thermoresponsive hydrogels based on Poloxamers 407/188 was considered in this new study. The effect of the EM on the hydrogel gelation temperature and time, rheological behavior, viscosity, spreadability and cutaneous permeation was evaluated. Hydrogels containing the EM led to a significant reduction in gelation temperature (25.67-29.67°C vs. 38.00°C for the control), faster sol-gel transition (118.67-153.33 s), increased gel strength and viscosity, suggesting stronger micellar interactions within the poloxamer network. Despite the higher viscosity, EM hydrogels achieved a nearly twofold increase in cumulative IBU permeation compared to the control, which was associated with improved drug solubilization and the permeation-enhancing effect of menthol. In summary, the incorporation of the EM into hydrogels presenting emulsifying properties proved to be an effective approach for overcoming biopharmaceutical issues, beside improving gel properties and simplifying the production process. Given the benefits achieved, this approach could also be explored for other poorly water-soluble molecules to be incorporated into aqueous topical formulations, ensuring substantial advances in this field.