DEVELOPMENT AND IN VITRO-IN VIVO EVALUATION OF GLIPIZIDE LOADED MULTIUNIT PULSATILE FORMULATION FOR TREATMENT OF DIABETIC PATIENTS

The aim of the present study was to develop oral multiparticulate pulsatile drug delivery system for hypoglycemic agent ‘glipizide'. Time dependent rupturable system was selected for delivering glipizide in a pulsatile pattern. In the present study, two types of particles were prepared i. e. Type 1 (immediate release type) and Type 2 (delayed release type). Extrusion and spheronization process was selected to prepare particles, wherein lactose and microcrystalline cellulose mixture (2:1) was used as processing aid. Various parameters of extrusion and spheronization process were optimized in order to meet desired particle size distribution, shape and flow properties. Immediate release Type 1 particle was optimized to achieve more than 80% drug release within 30 min for which surfactant approach was employed to overcome the dissolution rate related issue of the glipizide. Delayed release pattern of Type 2 particles was achieved by coating hydroxypropylmethylcellulose and ethyl cellulose. Various coating parameters were optimized to attain efficient coating of the particles. Different concentrations of hydroxypropylmethylcellulose (5 and 3.5% w/w E-15 grade) and ethyl cellulose (5 and 3% w/w) were studied for release pattern for Type 2 particles. Final formulation was characterized using for particles size, flow properties and surface morphology. To examine the drug release, dissolution studies were performed. Pharmacokinetics studies in Sprague Dawley rats reveal improved oral bioavailability of glipizide following oral administration