Optimization and Evaluation of Microsponge-Embedded Thermoresponsive In-Situ Gel for Intranasal Delivery of Sumatriptan Succinate

Migraine is a prevalent neurological disorder requiring rapid and effective therapeutic intervention. However, the conventional oral administration of Sumatriptan succinate (SS) is limited by extensive first-pass metabolism, low bioavailability, and a short biological half-life. This study aimed to develop and optimize an SS-loaded microspongeembedded thermoresponsive In-Situ nasal gel to prolong nasal residence time and provide sustained drug release for improved migraine management. SS-loaded microsponges were prepared by the quasi-emulsion solvent diffusion method using ethyl cellulose as the polymer and polyvinyl alcohol as the stabilizer. A 2² factorial design was employed to optimize the formulation by evaluating the effects of polymer concentration and stirring speed on particle size, drug entrapment efficiency (DEE), and drug content. The optimized microsponges were incorporated into Poloxamer 407based In-Situ gels (15%, 20%, and 25% w/v) prepared by the cold method and evaluated for physicochemical characteristics, pH, viscosity, gelation temperature, gelation time, and in vitro drug release. The microsponges exhibited particle sizes of 50.45–83.52 µm, DEE of 48.20–77.32%, and drug content of 59.20–68.63%. SEM analysis confirmed spherical, porous microsponges with sustained drug release (64.19–74.33%). The In-Situ gels demonstrated an acceptable pH (4.98–5.26), gelation temperature (28.7–33.2°C), rapid gelation time (29–36 s), and viscosity ranging from 3509 to 3699 cPs. The optimized formulation (ISG 3) exhibited sustained drug release (39.45% in 8 h) following zero-order kinetics (R² = 0.9883) and remained stable over 3 months. These findings suggest that the microspongeembedded thermoresponsive In-Situ nasal gel is a promising platform for sustained intranasal delivery of SS, with the potential to improve therapeutic efficacy and patient compliance in migraine management.