A hydrogel miscible azelaic acid-ionic liquids for the treatment of acne vulgaris: Enhanced solubility and skin retention

Abstract

Azelaic acid (AzA) is a natural dicarboxylic acid used to treat acne vulgaris but is greatly limited by poor aqueous solubility. This study aims to enhance the solubility and skin retention of AzA by ionic liquids (ILs). AzA-ILs were synthesized by a decomposition reaction with amine compounds. AzA-ILs synthesized with Tris-(hydroxymethyl)-aminomethane ([AzA][Tris]) and meglumine ([AzA][Meg]) at a molar ratio of 1:2 were liquid at room temperature and miscible with water. ¹H-NMR and FT-IR confirmed the synthesis of AzA-ILs. [AzA][Tris] got higher transdermal transport and skin retention of AzA than [AzA][Meg]. ZEN has a lower viscosity and better spreadability than Carbomer and thus was adopted as the gel matrix. [AzA][Tris] was also miscible with the ZEN matrix at any concentration. Hydrogels containing 10% (w/w) AzA exhibited the highest transdermal transport and skin retention among hydrogels with higher or lower concentrations of AzA. AzA-IL hydrogel (10%, w/w) obtained similar therapeutic efficacy but lower skin irritation than the Finacea® (a marketed hydrogel of 15% AzA). In conclusion, ILs greatly enhanced the aqueous solubility of AzA to develop transparent hydrogel and skin retention to achieve good treatment for acne vulgaris.