Salicylate-Based Ionic Liquids as Innovative Ingredients in Dermal Formulations

J Pharm Sci. 2021 Sep 23;S0022-3549(21)00499-8. doi: 10.1016/j.xphs.2021.09.028. Online ahead of print.


The identification and characterization of novel compounds with improved functionality and safety is of great importance. Ionic liquids are potential candidates for use in dermal formulation as multifunctional components with a large variability potential. The behavior of Ionic Liquids (ILs) in aqueous solutions has an impact on their functionality in the formulation as well as on their biological activity. Therefore, the solutions of selected ILs containing salicylate anions were investigated in the present work. The alkyl chain length of the cation determined most of the studied parameters. Thus, the surface activity, the antimicrobial activity, and cytotoxicity were directly proportional to the chain length. The salicylate anion did not affect the surface activity significantly, but had an important influence on the biological activity, especially for ILs with short chain lengths. It was found that the antimicrobial activity of benzalkonium-based ILs was mainly dependent on the cation, and the minimal inhibitory concentration (MIC) values were three order of magnitude lower than those of salicylic acid. Nevertheless, the slightly lower MIC values of benzalkonium salicylate, compared to benzalkonium chloride, might indicate a synergistic effect resulting from different modes of action of the two ions. N-hexyl nicotinamide salicylate also showed a higher antimicrobial activity than salicylic acid and, at the same time, a very good skin tolerance at concentrations up to 5% w/w. Based on our investigations N-hexyl nicotinamide salicylate was identified as potential emulsifiers / co-emulsifiers with antimicrobial properties for dermal formulations.

Keywords: Antimicrobial activity; Cytotoxicity; Ionic liquids; N-hexyl nicotinamide; Salicylate; Surface activity.