Preparation and Optimization of Fast Dissolving Film of Naratr iptan Hydrochloride.

Abstract

BACKGROUND Naratriptan is second-generation triptan class of antimigraine drug which selectively bind with 5-HT(1B/1D) receptor. It is widely used to treat the migraine attack due to its better tolerability and lower recurrence rate as compared to other triptans. Despite of the applicability, Naratriptan also have several drawback like slow onset of action and fist pass metabolism which reduce its efficacy. In order to increase the efficacy of naratriptan fast dissolving film is prepared. METHOD Fast dissolving film of Naratriptan hydrochloride was prepared by solvent casting method Based on the patent survey (US 7648712 B2, WO 2012053006 A2, US 20090047330 A1, EP 2821066 A4, WO 2008108940 A1, WO 2010151020 A3) excipients were screened to find out suitable combination of polymer and plasticizer and Hydroxypropylmethyl Cellulose (HPMC E6) and glycerol were selected as film forming polymer and plasticizer respectively. To study the effect of independent variables on dependent variables 32 full factorial design was applied using Concentration of HPMC E6 and Concentration of Glycerol as independent variables and disintegration time, folding endurance, tensile strength and cumulative % drug release at 2 min as dependent or response variables. A statistical model incorporating interactive and polynomial terms was utilized to evaluate the responses. Result & Conclusion: From the results of statistical evaluation batch F3 was selected as the optimized batch which exhibited shorter disintegration time (22sec) with satisfactory mechanical properties (tensile strength 652.17 gm/mm2). Dissolution of drug from F3 formulation was rapid with around 91% drug release in 120sec. Optimized batch was further evaluated for in vitro permeation study using Franz diffusion cell.