Multiple - Unit Floating Drug Delivery System for Gastric Retention of Weakly Acidic Drug

Abstract:

The objective of the work is to develop a multiple-unit-type of oral floating drug delivery system to prolong the gastric residence time and increase the bioavailability of weakly acidic drugs, which has absorption window in the gastric region. Floating alginate beads were formulated using Glipizide, an oral antidiabetic drug as a model. The beads were prepared by dispersing Glipizide with various gas forming agent (Calcium Carbonate, Magnesium Carbonate, Sodium Bicarbonate, Sodium Carbonate, Potassium Bicarbonate and Potassium Carbonate) into sodium alginate solution and then dripping the dispersion into an acidified solution (10 % glacial acetic acid) of calcium chloride. The alginate beads were formed due to ionotropic gelation by calcium ions. The carbon dioxide developed from the reaction of carbonate salts with acid permeated through the alginate matrix, to form pores, which provided the beads buoyancy. The beads were evaluated for size, mechanical strength, floating lag time, total floating duration, in-vitro dissolution and release kinetics. The formulations were prepared with different gas forming agents and were optimized for different weight ratios of gas forming agent and sodium alginate. The beads containing higher amounts of Calcium carbonate showed good floating behavior with required release of the drug. The formulation was subjected to In-vivo X-ray studies in healthy male rabbits which showed the position of beads in the upper part of the stomach. The confirmation of In-vivo floating behavior made them as a suitable candidate for Multiple-Unit Floating Drug Delivery System.

Keywords: Glipizide, Floating Beads, Gas forming agents, Multiple-unit Floating Drug Delivery System