BRAIN TARGETING OF FLUNARIZINE HYDROCHLORIDE BY SOLID LIPID NANOPARTICLES FOR PROPHYLAXIS OF MIGRAINE Mandal Surjyanarayan*, Shah Pratik, Shah Gunjan, Khatri Doli,

Flunarizine hydrochloride, a piperazine derivative, is a selective Ca channel blocker coupled with its antihistaminic property claimed to be effective in prophylaxis of migraine. Oral bioavailability of Flunarizine hydrochloride is very low (less then 18%) due to poor water solubility and extensive first pass metabolism. Hence the aim of the present study was to develop Flunaruzine hydrochloride loaded sold lipid nanoparticles to improve drug diffusion profile and hence the oral bioavailability. Flunarizine hydrochloride nanosuspension stabilised by poloxamer F-68 was first prepared by high speed homogenization and was lyophilized to obtain nanoparticle using mannitol (1:1 w/v) as cryoprotectant. Developed nanoparticle was characterized for its particle size and size distribution, drug content and % drug entrapment. In vitro dissolution study using dissolution bag (12000 D) and ex vivo study in rat ileum were carried out using simulated intestinal fluid as dissolution medium. Droplet size, Zeta potential, % drug content and % drug entrapment of the nanoparticles of the Flunarizine hydrochloride were found to be 282±50nm with PdI=0.424±0.028, 34.9±7.36mV, 98.3±0.26% and 67±0.55% respectively. In vitro, ex vivo permeation study revealed that cumulative percentage drug permeated was found to be 75.66±0.9% and 69±1.4% in 8 hrs. Data of the ex vivo release study indicated that drug release was controlled by combination of lipid swelling, erosion and diffusion through the hydrated lipid matrix. From the results it could be considered that the developed Flunarizine hydrochloride nanoparticles may be an alternative for the prophylaxis of migraine.