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

Abstract

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) × 3 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®. Medicated films were prepared after addition of 35 mg SS to each of the two selected plain formulae (F6 and F7) having desirability values above 0.9 showing the values of: 0.038, 0.039 kgf/mm(2) and 156.24, 164.16% and 0.0248, 0.0240 kgf/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 tmax (0.25 h) compared to Imitrex® tablet 25 mg (2 h) which is considered promising especially for the rapid relief of acute migraine attacks.

Orodispersible dosage forms: biopharmaceutical improvements and regulatory requirements

“…As an example, the administration of piroxicam, 181 as a freeze-dried tablet, gave a much faster absorption rate during the first hour after dosing (t lag = 21.6 182 min) than the capsule formulation (t lag = 59.4 min), although the bioavailability of the two formulations was 183 similar [3]. Moreover, a significant reduction of the t max values was found as in the case of valsartan [41] or 184 sumatriptan [42]. Table 1 compares the main pharmacokinetic effects related to the administration of 185 conventional dosage forms or ODx.…”

Application of Quality by Design Approach for the Optimization of Orodispersible Film Formulation

“…Activation of 5-HT 1B receptor, which is present on the vascular smooth muscles, causes vasoconstriction of smooth muscles [16]. Activation of 5-HT 1D which is located on the sensory trigeminal terminals inhibits the release of sensory and vasoactive neuropeptides and vasodilator transmitters [17,18].…”

A Review on Fast Dissolving Systems: From Tablets to Nanofibers

“…They can also be used to treat localized conditions in oral cavity due to their mucoadhesive property (125) as well as systemic absorption (28,29). Encapsulating drugs as nanofibers enhances the bioavailability of drugs due to faster disintegration and dissolution (45,126,127). Furthermore, insoluble or swellabe polymers are used in nanofibers to control the drug release (42,120).…”