Thermotriggered intranasal microemulsions for nose to brain targeting of rizatriptan

摘要

Thermotriggered mucoadhesive (TTM) microemulsions were developed for nose to brain targeting of antimigraine drug, rizatriptan benzoate (RB). Intranasal TTM microemulsions were developed by spontaneous emulsification technique. Thermosensitive polymers like Pluronic F127 and Pluronic F68 were tried out to modulate the gelation of microemulsion formulations at physiological temperature after intranasal administration. Various mucoadhesive polymers were tried out in optimized thermo-triggered microemulsion formulations. The mucoadhesion force in terms of detachment stress determined using sheep nasal mucosa was higher with 0.05% w/v of Carbopol 980. TTM intranasal microemulsion was optimized based on permeability parameters such as steady-state flux, permeability coefficient and enhancement ratio. After a single dose administration (4mg/kg), the plasma concentration peaked at 15 min and the absolute bioavailability was about 94.84%. The uptake of RB in the brain from the nasal route was three folds, compared with intravenous (z.v.) injection. The ratios of AUC in whole brain tissue to that in plasma obtained after nasal administration were significantly higher than those after i.v. administration. These results suggest that TTM microemulsions have potential for nose to brain targeting of rizatriptan benzoate.