<p>An innovative centrally acting analgesic, tapentadol works by inhibiting norepinephrine reuptake and agonising mu-opioid receptors. Tapentadol&#39;s oral use is restricted by gastrointestinal adverse effects and first-pass metabolism. We used Poloxamer 407 and Carbopol 934 to create a topical thermosensitive gel formulation in order to get around these restrictions. In order to give long-lasting and targeted pain relief, the goal was to create an in-situ gelling system that stays liquid at room temperature and turns into a gel at skin temperature. pH, viscosity, gelation temperature, spreadability, drug content, in vitro drug release, ex vivo skin penetration, and stability were all assessed for the produced gel. The improved formulation showed good penetration properties, a gelation temperature of 32&plusmn;0.5&deg;C, and sustained drug release of up to 89.2% after 8 hours. According to these results, thermosensitive gel filled with tapentadol presents a viable substitute for regional pain management.</p>