The present study aimed to evaluate the influence of chemical modifications on the properties of flurbiprofen derivatives, focusing particularly on their skin permeation and accumulation. Comprehensive characterization of all synthesized compounds was conducted using NMR, FTIR, and HRMS for structural analysis. Crystallinity was assessed via XRD, while thermal stability and properties were evaluated using TG and DSC, respectively. In addition, solubility in water, organic solvents, and PBS, as well as lipophilicity, were examined to better understand their physicochemical behavior. Biological properties were investigated through antioxidant and anti-inflammatory activity assessments, along with cytotoxicity evaluations. The study specifically tested a flurbiprofen salt, which combined the flurbiprofenate anion with the menthyl ester of the L-alanine cation. Comparisons were made with unmodified flurbiprofen to evaluate differences in skin permeability and accumulation. Several mixtures of individual substrates (L-alanine, menthol, and L-alanine menthyl ester hydrochloride) with flurbiprofen were also prepared, with some forming eutectic mixtures. Results indicated that both the eutectic mixtures and the flurbiprofen derivative, L-alaninium menthyl ester flurbiprofenate, exhibited significantly enhanced skin permeation and accumulation, reaching levels 1.5-2.5 times higher than unmodified flurbiprofen. These findings underscore the effectiveness of chemical modifications in improving flurbiprofen's transdermal delivery potential, especially via eutectic mixtures, which appear to play a critical role in enhancing skin permeability. Consequently, this study supports the potential of tailored chemical modifications in developing more effective and controlled transdermal therapies.
Keywords: Anti-inflammatory activity; Eutectic mixtures; Flurbiprofen; Skin permeability; Terpene esters; Transdermal delivery.
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