Development and evaluation of floating gastro-retentive in situ gel for oral delivery of leflunomid

Juvenile idiopathic arthritis (JIA) is a chronic autoimmune —inflammatory disease. It affects up to 1to 4 per 1,000 children worldwide. Leflunomide (LEF) is a disease modifying anti-rheumatic drug (DMARD) which effectively reduces the signs and symptoms of active JIA in children and rheumatoid arthritis (RA) in adults. The objective of the present study was to develop and evaluate an oral floating in situ gel of LEF as liquid gastro-retentive drug delivery system to improve patient compliance, reduce dosing frequency, increase residence time of drug in the stomach and sustain drug delivery of LEF using different release retardant polymers. The prepared gels were characterized for viscosity, drug content, pH, density, gelling strength, invitro gelling and floating studies and in-vitro release study. Concentration of used polymers significantly affected the formulation viscosity, floating behavior and in-vitro drug release. Analysis of the release kinetic data showed that the drug release from in situ gel followed zero order except formulae containing HPMC which exhibited Higuchi's diffusion model. Considering the in-vitro release, viscosity, floating lag time (FLT) and stability studies, formula F2 (containing 0.4%HPMC K100M) was considered the best formula since it showed minimum floating lag time (36 sec), optimum viscosity (230.5 cps) , optimum drug release (97.34%) after 24 hand has the highest t90 value (205.17 days). Therefore, it was chosen for further ex-vivo study in rats to detect gel formation in the stomach. It showed good gel formation. Hence, floating in situ gelling system is considered a novel approach to sustain drug delivery of LEF.