Thermosensitive, mucoadhesive brivaracetam nasal gel: a promising strategy for targeted relief of epilepsy.

This study aimed to develop a mucoadhesive thermosensitive in situ nasal gel of brivaracetam (BRIVA-gel) to treat epilepsy. A BRIVA-gel was statistically optimized using 3 factorial design varying amounts of Poloxamer 407 and Carbopol 934. The formulation was subjected to nasal ciliotoxicity studies. A comparative pharmacokinetic and brain distribution study was also conducted on BRIVA-gel and oral-marketed tablets in rats. The final BRIVA-gel was clear in the sol form and transformed into a gel at 32-34 °C with a gelling time between 49 and 154 s. The drug release studies demonstrated the sustained release of BRIVA-gel up to 4 h. Stability studies confirmed the BRIVA-gel was stable over a 3-month testing period at refrigerated conditions. BRIVA-gel did not show any nasal toxicity and was considered safe for intranasal delivery. The pharmacokinetic study in rats exhibited a twofold increase in AUC by BRIVA-gel (25.907 µg/mL.h) than the oral-marketed tablets (11.844 ng/mL.h). The brain biodistribution revealed significantly improved drug content in the brain by nasal BRIVA-gel than oral tablets. These findings suggested that thermosensitive in situ nasal BRIVA-gel has the potential to serve as a targeted delivery system to the brain, overcoming the challenges of first-pass metabolism and gastric degradation.