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. 2025 Oct;398(10):14301-14313.
doi: 10.1007/s00210-025-04172-1. Epub 2025 Apr 26.

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

Bhavya Narang  1 , Kalyani Barve  1 , Sarika Wairkar  2
Affiliations

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

Bhavya Narang et al. Naunyn Schmiedebergs Arch Pharmacol. 2025 Oct.

Abstract

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 32 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.

Keywords: Brivaracetam; Epilepsy; In situ gel; Nose-to-brain targeting; Thermosensitive.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Animal Ethics Committee of NMIMS University in Mumbai, India (protocol number CPCSEA/IAEC/P- 93/2022). Consent for publication: The manuscript has been read and approved by all the authors. Competing interests: The authors declare no competing interests.

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