Formulation and evaluation of thermoreversible mucoadhesive in-situ gel for intranasal delivery of naratriptan hydrochloride

Intractable migraine presents a significant treatment challenge due to associated throbbing or pulsating headache, which affects one half of the head and lasts from 2 to 72 h. Naratriptan hydrochloride is an approved drug molecule for migraine headaches, but its use is limited due to its poor bioavailability, reoccurrence of migraine and lesser half-life requiring frequent dosing. Therefore, the objective of present study was to formulate a thermoreversible intranasal gel for drug targeting directly to brain via olfactory lobe pathway thereby improving bioavailability. Gels were formulated by using poloxamer 407 as thermoreversible polymer and carbopol 934 as mucoadhesive polymer. Formulated gels were characterized for gelation temperature, gel strength, mucoadhesive strength, viscosity, in-vitro drug release and ex-vivo permeation study using sheep nasal mucosa. In-vitro and ex-vivo drug release studies suggested that the release rate was directly proportional to the concentration of carbopol 934, whereas poloxamer 407 reduced the rate of drug release. Histopathology study of sheep nasal mucosa showed no signs of damage to columnar epithelial cells, confirming non-toxic nature of the formulated gel. Stability studies performed as per ICH guidelines [Q1A (R2)] suggested that the gels were stable.