Development and Evaluation of an Innovative S‐Flurbiprofen‐Diethylamine Emulgel With Superior Transdermal Delivery and Analgesic Activity

ABSTRACT This study aimed to develop an innovative (S‐flurbiprofen)‐diethylamine (SFP‐DEA) emulgel formulation via incorporating SFP as the active pharmaceutical ingredient within a carbomer 940 gel matrix. SFP‐DEA emulgel was synthesized by dissolving SFP‐DEA in the aqueous phase of an oil‐in‐water (O/W) emulsion, followed by dispersion into a carbomer 940 gel matrix. The physicochemical stability of SFP‐DEA emulgel was evaluated via centrifuge, temperature swing test, high temperature, and long‐term storage at ambient conditions. Ex vivo SFP transdermal delivery of SFP‐DEA emulgel was evaluated using a Franz diffusion cell combined with excised rat skin. The in vivo analgesic activity and skin irritation test of SFP‐DEA emulgel were evaluated using a mouse knee osteoarthritis model and healthy rats, respectively. Results demonstrated that SFP‐DEA emulgel showed robust physicochemical stability and retain a final SFP content of 1.5% (w/w). Ex vivo transdermal study demonstrated that EMG5 (the emulgel optimized with laurocapram and menthol as penetration enhancers) achieved an 8‐h cumulative SFP transdermal flux of 741.28 μg/cm 2 (44.23% of the administered dose), which is 27.94‐fold higher than that of Loqoa (SFP tapes). In addition, SFP‐DEA emulgel demonstrated rapid analgesic efficacy, with an 84.36% pain inhibition rate within 30 min in the osteoarthritis model, and elicited no signs of skin irritation in rats. In conclusion, the SFP‐DEA emulgel developed herein exhibits high stability, enhanced transdermal delivery, preliminary analgesic activity, and favorable safety profiles, positioning it as a promising topical therapeutic candidate.