TPGS stabilized sublingual films of frovatriptan for the management of menstrual migraine: Formulation, design and antioxidant activity

This work has been carried out to formulate and optimize mucoadhesive sublingual films of Frovatriptan succinate monohydrate (FSM) using hydroxyethylcellulose (HEC) by solvent casting method. Frovatriptan has low bioavailability (∼27%) due to high first pass metabolism and lowest efficacy in 2 h pain free response among other triptans due to slow onset of action. Sublingual administration will improve the bioavailability of FSM by providing direct access to systemic circulation bypassing high first-pass effect with rapid absorption and instant onset of action. Prepared sublingual films were then evaluated for weight variation, thickness, surface pH, content uniformity, mechanical and mucoadhesive properties, swelling index, in vitro drug release and permeation studies. Various permeation enhancers were also tried to improve the permeation of drug through sublingual mucosa. Among different permeation enhancers, Polysorbate 80 at 2% v/v in film showed highest permeation of drug (around 100% at 2 h) with highest Jss and Kp of 223.77 μg/cm2 hr and 0.179 cm/h respectively through sublingual mucosa. Finally, TPGS (d-α-tocopherol polyethylene glycol succinate 1000) was loaded in Polysorbate 80 (2% v/v) films to further enhance drug permeability and provide antioxidant properties.

279