Ionic liquids in transdermal drug delivery system: Current applications and future perspectives

The transdermal drug delivery (TDD) shows considerable advantages over other administration pathways. However, conventional enhancing permeation methods face a series of challenges owing to barrier function provided by the skin, of which enhancing abilities either are so strong that it results in toxicity and irritation, or too weak to achieve desirable therapeutical effects. To address these issues, it is an urgent need to develop a novel method to overcome the limitations of current measures. Fortunately, in the preceding decades, ionic liquids (ILs) have been extensively studied and increasingly applied in pharmaceutical drug delivery due to their unique physicochemical and biological properties. What is more, tunability of structure resolves the challenges in processing active pharmaceutical ingredient (API) formulation, such as polymorphism and poor solubility of drugs. Thus, the presence of ILs provides an ample design space for the transdermal drug delivery system (TDDS). This review discusses the shortcomings of conventional enhancing permeation methods and introduces the application of ILs in transdermal delivery from three aspects: i) ILs are applied as enhancers to weaken the barrier function of the stratum corneum (SC). ii) As counterions, ILs are combined with API to modify the physicochemical properties of drugs. iii) ILs assist in the design of transdermal preparation for perfecting formulation. This review comprehensively introduces the major breakthroughs made in the applications of ILs, which can serve as guidance to provide novel ideas for formulation scientists who hit the bottleneck in the development of TDD.