Mechanistic Study of Release Characteristics of Two Active Ingredients in Transdermal Patch Containing Lidocaine−Flurbiprofen Ionic Liquid

Ionic liquids (ILs) have been proven to be an efficient technology for enhancing drug skin permeability. However, the question of whether the two components of ILs are released synchronously in transdermal preparations has remained unclear. Thus, this study aimed to investigate the release characteristics of two components of ILs and their underlying molecular mechanism. The ILs containing flurbiprofen (FLU) and lidocaine (LID) were synthesized and characterized. The four typical acrylates pressure sensitive adhesives (PSAs) with different functional groups were synthesized and characterized. The effects of PSAs on the release characteristics of two components of ILs were investigated by drug release tests and verified by skin permeation experiments. The action mechanisms were revealed by FTIR, Raman, dielectric spectrum, and molecular docking. The results showed that the average release amount of FLU (0.29 μmol/cm(2)) and LID (0.11 μmol/cm(2)) of ILs in the four PSAs was significantly different (p < 0.05), which illustrated that the two components did not release synchronously. The PSA−none and PSA−OH with low permittivity (7.37, 9.82) interacted with drugs mainly by dipole-dipole interactions and hydrogen bonds. The PSA−COOH and PSA−CONH(2) with high permittivity (11.19, 15.32) interacted with drugs mainly by ionic bonds and ionic hydrogen bonds. Thus, this study provides scientific guidance for the application of ILs in transdermal preparations.