Formulation and Evaluation of Flexible Liposome Embedded In Situ Thermoreversible Intranasal Gel of Rizatriptan Benzoate

Abstract

The present study deals with formulation and evaluation of flexible liposome embedded thermoreversible in situ intranasal gel of rizatriptan benzoate. The flexible liposomes were formulated (F1-F9) and optimized with respect to percentage of ethanol and phospholipid to get optimum vesicle size and entrapment efficiency. The vesicles were characterized for their size, shape and zeta potential. The optimized stable vesicles were incorporated into in situ thermoreversible gel. The ex vivo permeation of drug through goat nasal mucosa was studied. The nasal mucosa used for drug permeation experiment was subjected to histopathological study to check for any damages. The in vivo pharmacokinetic study was carried out in Wistar rats. Vesicles size and entrapment efficiency of stable formulations (F2-F6) was varied from 71.2±14.16 to 199.3±26.03 nm and 72.98 % to 77.44 % respectively. The liposomes were nearly spherical in shape with zeta potential varied from -14.2±4.48 to -11.7±5.26 mV. The improved drug permeation and higher flux across nasal mucosa with enhancement ratio of 2.75 was observed for flexible liposomal thermoreversible gel F2 compared to normal thermoreversible hydrogel of drug. The histopathological study of nasal mucosa revealed that there was no damage to epithelial layer and was found to be intact. The area under the curve of optimized formulation (F2) was 3.98 and 1.53 times more than oral drug solution and intranasal gel respectively, confirming improvement in bioavailability. Thus present study concludes that flexible liposome enriched thermoreversible, mucoadhesive in situ intranasal gel of rizatriptan benzoate is a safe and effective drug delivery system for treatment of migraine.