Development and Characterization of Febuxostat loaded floating beads as Gastro-Retentive Drug Delivery System in the treatment of Gout: A Statistical Approach

Abstract

Febuxostat is a BCS class-II drug, used in the treatment of gout. However, because of its lower solubility, a higher and more frequent dose of the drug is required in the treatment. Febuxostat is a BCS class-II drug, used in the treatment of gout. Therapeutic window of Febuxostat is at site of stomach. But because of its lower solubility, higher and frequent dose of drug is required in the treatment. The objective of this research was to develop and evaluate febuxostat-loaded floating beads as a gastro-retentive drug delivery system (GRDDS) to target drug release up to 24hr in order to enhance bioavailability. The objective of this research was to develop and evaluate febuxostat loaded floating beads as Gastro-retentive drug delivery system (GRDDS) to target drug release up to 24hr in order of enhancement of bioavailability. Gastro-retentive floating beads were formulated using the ionotropic gelation method. Screening of lipids was carried out based on the shape and texture of floating beads. Drug-excipient compatibility study was done using DSC analysis. Further optimization of gastro-retentive floating beads of febuxostat was performed by Box-Behnken design using gelucire 43/01, lactose, and soluplus as independent variables and %drug entrapment and %drug release after 24 hr as dependent variables. Evaluation of the optimized batch was performed for in vitro buoyancy, %drug entrapment, %drug release, FTIR, and SEM study. Gastro-retentive floating beads were formulated using ionotropic gelation method. Screening of lipids was carried out on the basis of shape and texture of floating beads. Drug-excipient compatibility study was done using DSC analysis. Further optimization of gastro-retentive floating beads of febuxostat was done by Box-Behnken Design using Gelucire 43/01, lactose, soluplus as independent variables and %Drug entrapment and %drug release after 24 hr as dependent variables. Evaluation of optimized batch was performed for in vitro buoyancy, %drug entrapment, %drug release, FTIR and SEM study. In the ANOVA, contour plots, and 3D surface plots, the optimized batch showed 93.95±0.29 % drug entrapment and 88.14±0.58 % drug release after 24 hr with 98%±1% in-vitro buoyancy. Overlay plots and checkpoint batches were accompanied to confirm the optimization. Polynomial equations proved the positive effect of lipids on drug entrapment and drug release. SEM images explained porous and microstructures on beads. From the ANOVA table, Contour plots and 3D surface plots, Optimized batch showed 93.95±0.29 %drug entrapment, 88.14±0.58 % drug release after 24 hr, with 98%±1% in-vitro buoyancy. Overlay plot and check point batches were accompanied to confirm the optimization. Polynomial equations prove positive effect of lipid on drug entrapment and drug release. SEM images explained porous and micro structure on beads. In conclusion, gastro-retentive febuxostat floating beads were successfully developed and characterized for once a daily dose with enhanced bioavailability and reduced cost of therapy. NA