Abstract

DEVELOPMENT, OPTIMIZATION AND COMPARATIVE PHARMACOKINETICS EVALUATION OF GLIBENCLAMIDE BUOYANT TABLET FORMULATION

Suad Y. Alkarib*, Abubakr O. Nur, Zuheir A. Osman, Basheir I. Osman

ABSTRACT

This study address utilization of medium viscosity grade hydroxypropyl methylcellulose (HPMC, 4000cps), polyvinyl pyrollidone, stearyl alcohol, magnesium stearate and varying compression load to develop and optimize glibenclamide gastric floating tablets capable to float and sustain the release of loaded drug over a prolonged time duration in simulated gastric fluid through consecutive application of Box-Wilson and composite index designs. Time for floating onset, initial drug release and time for 50% drug release were found to be influenced by tablet hardness in linear fashion and by stearyl alcohol content in quadratic manner (p< 0.05 at CI95% for all influences) whereas floating duration confirmed to be affected by content of magnesium stearate and the joined influence of Mg stearate-sterayl alcohol content levels (p= 0.018 and 0.041 at CI95%, respectively). Glibenclamide floating tablet comprises of 46.7% w/w HPMC as matrixing agent, 16.7% stearyl alcohol as buoyancy enhancer, 2% magnesium stearate as lubricant, stated content of polyvinyl pyrollidone and compressed to 50N hardness was considered as best ranked formulation that fulfill preset constraints for floating onset (immediate floating), floating duration (6hrs), drug release in the first hour (28%), drug release within 6 hours (84%) and time for 50% drug release (3.2hr). Compared to an immediate release non floating glibenclamide tablets, in vivo investigation in 16 healthy human subjects revealed that glibenclamide plasma concentrations from floating tablet were maintained with less fluctuations over 24 hrs. Moreover, significant increase in Tmax, AUC0-∞, t½ and MRT of glibenclamide was measured with the optimized floating tablet formulation (p<0.004 at CI90% for these parameters), indicating persistence in duration of glibenclamide plasma concentration from floating tablet formulation.

Keywords: Glibenclamide, Floating tablets, In vitro investigation, In vivo evaluation, Comparative pharmacokinetics.