Preparation And Evaluation Of Thermo Sensitive In Situ Nasal Gel Of Rizatriptan For Brain Targeting

Abstract

Migraine is a highly prevalent neurological disorder characterized by recurrent, debilitating headaches and associated symptoms such as nausea, photophobia, and phonophobia. Conventional oral formulations of rizatriptan, a selective 5-HT₁B/₁D receptor agonist, are limited by delayed onset of action, low bioavailability due to hepatic first-pass metabolism, and poor absorption during migraine-induced gastric stasis. To address these challenges, this study aimed to develop and evaluate a thermosensitive in situ nasal gel of rizatriptan for targeted brain delivery. The formulation was prepared using poloxamer 407 and 188 as thermoresponsive polymers, with Carbopol 934P as a mucoadhesive agent to enhance nasal retention. The gel exhibited a sol–gel transition at nasal cavity temperature, ensuring ease of administration and prolonged mucosal residence. Physicochemical evaluations demonstrated suitable viscosity, pH, and drug content. In vitro release studies revealed sustained drug release, best described by the Korsmeyer-Peppas model, indicating anomalous transport. Ex vivo permeation studies using sheep nasal mucosa showed significantly enhanced drug transport compared to conventional solutions, and histopathological evaluation confirmed the safety and biocompatibility of the formulation. Comparative analysis with existing oral and nasal formulations highlighted the superior performance of the thermosensitive gel in terms of faster onset, higher bioavailability, and improved patient compliance. Overall, thermosensitive in situ nasal gels offer a promising platform for brain-targeted delivery of rizatriptan, paving the way for improved therapeutic outcomes in migraine management.