Structural transformation and drug delivery in transdermal patches based on ionic liquid-based microemulsion

Ionic liquids (ILs) have been extensively studied as part of transdermal drug delivery systems. However, the integration of IL-based formulations into pressure-sensitive adhesives (PSA) remains largely unexplored. In this report, we investigate an IL-in-oil (IL/O) microemulsion-based adhesive transdermal patch (ILP), with a focus on structural transition. Initially, four IL/O microemulsions with different concentrations of IL and surface-active IL (SAIL) were prepared and three (IL/O 1, IL/O 2, and IL/O 4) were chosen based on their particle size (<100 nm). The selected IL/O microemulsions were then blended with PSA (DURO-TAK 87-4098) at an equal ratio and dried at either 25 °C or 60 °C to form ILP1, ILP2, and ILP4. Small-angle X-ray scattering (SAXS) results demonstrated that incorporation of IL/O into the adhesive induced a structural transition, forming a liquid crystal-like lamellar structure with d spacings of 5.44–6.21 nm. Both IL/O composition and drying temperature play an active role in the intensity and peak positions of the SAXS profiles of ILPs. In vitro skin penetration study revealed that all ILPs significantly increased skin penetration compared to control patch. ILP2 achieved the highest acyclovir permeation (3.20 μg/cm 2 ), outperforming ILP1 (2.03 μg/cm 2 ) and ILP4 (1.85 μg/cm 2 ). These findings highlight the significant role of ILP composition in modulating structural transitions and enhancing drug delivery performance, offering valuable insight into the design of IL-based adhesive transdermal patches. • ILPs with different concentration of IL and SAIL were prepared and characterized. • SAXS measurement revealed that ILPs undergo structural transition. • Composition and preparation temperature of the ILPs influence the SAXS profile. • Presence or absence of drug does not have any impact on SAXS profiles. • Increase in SAIL concentration of ILP improves skin penetration.