Robustness testing of a modified-release tablet formulation comprising metformin and glibenclamide

Abstract

It was recently ascertained that sulphonylureas and biguanides synergistically act for the control of blood glucose levels in patients with type II diabetes, by different pharmacological mechanisms. The aim of this study is to design a modified release formulation comprising metformin hydrochloride and glibenclamide, where one drug does not affect the release of the other drug. Due to a relatively high unit dose of metformin, the tablets should be size fitted for oral administration and should ensure the controlled release of the two active ingredients. Taking into consideration the poor flowability of metformin hydrochloride, in order to attain dose uniformity, a wet granulation manufacturing process was used. Glibenclamide was geometrically dispersed into the granules of metformin. The mixture was blended with soluble filler, a hydrophilic polymer, a desintegrant and a lubricant. The hydrophilic polymer used was: hydroxypropylcellulose (Klucel® HF, HXF) and hydroxymethylpropylcellulose (Methocel® K100 LV CR, K4M and E4M). The matrix tablets were evaluated for their robustness: hardness, friability, thickness, and weight variation and disintegration time. It was concluded that satisfactory robustness profiles can be achieved using all types of hydrophilic polymers, by wet granulation of the major active ingredient, followed by a direct compression into a modified release matrix. Keywords: metformin hydrochloride, glibenclamide, diabetes, formulation, matrix tablets.