Enhanced transdermal delivery of S-flurbiprofen-lidocaine ionic liquid-loaded emulgel for synergistic anti-inflammation and analgesia.

An S-flurbiprofen (SFP)-lidocaine (LDC) ionic liquid (IL)-loaded emulgel (SFP-LDC-IL-EMG) was developed for enhanced transdermal delivery and synergistic anti-inflammation and analgesia. SFP-LDC IL was synthesized from SFP and LDC at a molar ratio of 1:1, dissolved in isopropyl myristate (IPM, oil phase) and incorporated into water phase to create a nanoemulsion. The nanoemulsion was then dispersed into sodium carboxymethyl cellulose (CMC-Na) gel matrix to form the final product of SFP-LDC-IL-EMG, which was characterized via rheology, morphology and stability in detail. Rheological assessment revealed that SFP-LDC-IL-EMG was a typical elastic gel with shear-thinning behavior, which maintains comparable viscosity and gel network integrity to blank emulgel. Ex vivo transdermal delivery of SFP-LDC-IL-EMG demonstrated 8 h cumulative permeation of 931.3 ± 68.7 µg/cm2 for SFP and 1094.2 ± 91.4 µg/cm2 for LDC, representing 4.5-fold and 3.3-fold enhancements over those of SFP-EMG and LDC-EMG. The in vivo therapeutic performance of SFP-LDC-IL-EMG was evaluated in a carrageenan-induced paw edema model, which revealed potent and rapid anti-inflammation with a peak paw swelling inhibition rate of 85.9 % and superior analgesic efficacy with maximum possible effect of 94.9 %. Histopathological examination of SFP-LDC-IL-EMG-treated animals showed minimal inflammatory cell infiltration with tissue morphology closely resembling normal groups. These findings establish SFP-LDC-IL-EMG as a promising topical delivery system combining IL-mediated transdermal enhancement with synergistic pharmacological mechanisms for effective localized inflammation and pain management.