Transdermal drug delivery systems (TDDS) show clear advantages over conventional routes of drug administration. Nonetheless, there are limitations to current TDDS which warrant further research to improve current TDD platforms. Spurred by the synthesis of novel biodegradable ionic liquids (ILs) and favorable cytotoxicity studies, ILs were shown to be a possible solution to overcome these challenges. Their favorable application in overcoming challenges ranging from synthesis, manufacture, and even therapeutic benefits were documented. In this review, said ILs are highlighted and their role in TDDS is reviewed in terms of (a) ILs as permeation enhancers (single agents or combined), (b) ILs in drug modification, and (c) ILs as active pharmaceutical ingredients. Furthermore, future combination of ILs with other chemical permeation enhancers (CPEs) is proposed and discussed.

Ionic liquids (ILs) have been touted as effective and environmentally friendly agents, which has driven their application in the biomedical field. The study compares the effectiveness of an IL agent, 1-hexyl-3-methyl imidazolium chloride ([HMIM]Cl), to current industry standards for plasticizing a methacrylate polymer. Industrial standards glycerol, dioctyl phthalate (DOP) and the combination of [HMIM]Cl with a standard plasticizer was also evaluated. Plasticized samples were evaluated for stress–strain, long-term degradation, thermophysical characterizations, and molecular vibrational changes within the structure, and molecular mechanics simulations were performed. Physico-mechanical studies showed that [HMIM]Cl was a comparatively good plasticizer than current standards reaching effectiveness at 20–30% w/w, whereas plasticizing of standards such as glycerol was still inferior to [HMIM]Cl even at concentrations up to 50% w/w. Degradation studies show HMIM-polymer combinations remained plasticized for longer than other test samples, >14 days, compared to glycerol <5 days, while remaining more pliable. The combination of [HMIM]Cl-DOP was effective at concentrations >30% w/w, demonstrating remarkable plasticizing capability and long-term stability. ILs used as singular agents or in tandem with other standards provided equivalent or better plasticizing activity than the comparative free standards.