Hidradenitis suppurativa (HS) has been considered an orphan disease with limited treatments available. The main topical treatment is clindamycin lotion; however, short retention and frequent application is the main setback. The aim of this study was to attain an optimized antibacterial in-situ spray formulation for the skin condition hidradenitis suppurativa, which gels once in contact with the skin surface of around 37⁰C and possesses bioadhesion as well as sustained-release properties. Different concentrations of thermo-reversible gelling polymer Pluronic F-127 were investigated along with the selected bioadhesive polymers, HPMC and SA. The optimized formulation F3 having 18% Pluronic F-127 with 0.2% HPMC and 0.2% SA was characterized based on various physicochemical properties. The gelation temperature of F3 was found to be 29.0 ± 0.50⁰C at a time 1.35 ± 0.40 min. F3 had the viscosity of 178.50 ± 5.50 cP at 25⁰C, and 7,800 ± 200 cP at 37⁰C as the gel set. The detachment force was found at 0.80 ± 0.041 N. More than 80% cell found viable after treating at 10 mg/mL. The pH measurement with 1% clindamycin was obtained at pH 5.8. Cumulative drug release was 73.80% in 8 h; the release pattern of drug followed zero-order kinetics with Higuchi release mechanism. The n-value obtained from Korsmeyer-Peppas model showed Fickian diffusion. Average zone of inhibition was 43.44 ± 1.34 mm. The F3 formulation showed to improve residence time and enhance sustained drug release.