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.
