A novel approach to sustain delivery of leflunomide from floating gastro-retentive in situ gel for treatment of juvenile idiopathic arthritis: development, in-vitro and in-vivo evaluation

Abstract

This study aimed to develop and evaluate a floating oral in situ gel with leflunomide (LEF) as a liquid gastro-retentive drug delivery system to increase the residence time of the drug in the stomach and sustain drug delivery. Floating in situ gel system of leflunomide was prepared using sodium alginate as a gelling polymer, calcium carbonate as floating agent and different polymers to extended release. The physicochemical properties of in situ gels of leflunomide were in the acceptable range. An analysis of the release kinetics showed that the drug release followed a zero order, except for the formula containing hydroxypropylmethylcellulose (HPMC), which followed Higuchi’s model. Formula (F2) (0.4% HPMC K100M) was considered the best formulation as it had a minimum FLT (36 sec), optimum viscosity (230.5 cps), optimum drug release (97.34%) after 24 h, and the highest t90 value (205.17 days). Therefore, formula (F2) was chosen for further ex-vivo and bioavailability studies. The pharmacokinetic parameters were compared to those of commercially tablets (Apetoid®), and F2 exhibited a relative bioavailability of 197.73%. The prepared floating in situ gel system is a novel approach which indicate a remarkable increase in the residence time of LEF in the stomach and sustain its delivery.