Preparation and physicochemical characterization evaluation of thermosensitive sumatriptan liquid suppository

Abstract

Background: Sumatriptan succinate is a 5-HT1b and 5-HT1d receptor agonist which is used in the treatment of migraine. It shows low bioavailability (15%) due to high hepatic first pass metabolism. Objective: The present work was undertaken to formulate thermosensitive sumatriptan liquid suppository with the objective of improving the therapeutic efficacy, patient compliance and bioavailability. Methods: A Box-Behnken design with three factors, three-level was used for the preparation of suppositories. Suppositories were formed using cold method with chitosan (anionic) and poloxamer 407 (unionic) as a thermogelling polymer. Response surface design was employed to study the effect of independent variables, chitosan (X1, 0.1-0.3%), Sumatriptan succinate (X2, 125-375 mg) and amount of poloxamer 407 (X3, 18-22 %w/v) on the dependent variables as gelation temperature, gel strength, Syringeability/injectability, drug content, pH, detachment force onto gel surface, release and permeation. Results: Selected formulations (as S₂) had a clear appearance in the sol form, with gelling temperature, detachment force, gel strength, drug content, syringability/injectability and pH surface showed that 32 ˚C, 732.48 N/cm², 5.9 mm, 4.5% and 6, respectively. Mucoadhesive strength was adequate to provide prolonged adhesion. In vitro drug release studies showed that release of S0 formulation (without chitosan) had faster release than the formulations prepared (with chitosan) as S2, S8, S11 and S13 had faster release (p<0. 05). Conclusion: From these findings it can be concluded that in situ thermosensitive sumatriptan succinate liquid suppository may be potential drug delivery system for sumatriptan succinate to overcome first-pass metabolism and there by to improve the bioavailability.