Sumatriptan succinate sublingual fast dissolving thin films: formulation and in vitro/in vivo evaluation

Sumatriptan succinate (SS) is a 5-HT1 receptor agonist used in the treatment of migraine having poor bioavailability (15%) due to its extensive first-pass effect. The aim of this work was to prepare SS sublingual fast dissolving thin films (SFDTFs) allowing the drug to directly enter the systemic circulation and bypassing the first-pass metabolism. Plain thin films were prepared using solvent casting technique adopting 2(3)x3 factorial design to study the effect of polymer and plasticizer type and concentration on mechanical properties and in vitro disintegration time of the plain prepared films using Design-Expert (R). Medicated films were prepared after addition of 35mg SS to each of the two selected plain formulae (F6 and F7) having desirability values above 0.9 showing the values of: 0.038, 0.039kgf/mm(2) and 156.24, 164.16% and 0.0248, 0.0240kgf/mm(2) as tensile strength, percent elongation and elastic modulus, respectively. PVP K30 was efficient as crystallization inhibitor in retarding SS crystallization. Pharmacokinetic study of the optimum formula F7 (PVP K30:SS (1:1 w/w)) in healthy human volunteers using LC/MS/MS revealed a shorter t(max) (0.25h) compared to Imitrex (R) tablet 25mg (2h) which is considered promising especially for the rapid relief of acute migraine attacks.