[Formulation by design of experiments of immediate release tablets with metformin hydrochloride and glibenclamide]

The present investigation was based on the latest quality by design principles, using the design of experiments technique. The aim was to attain an immediate release formulation of metformin hydrochloride and glibenclamide and to optimize the delivery of these two different antidiabetic agents within a single-tablet combination.

Due to the poor flow properties of metformin hydrochloride, in order to attain the dose uniformity, a wet granulation based manufacturing process was used. The prepared tablets were evaluated for the release of metformin hydrochloride and glibenclamide using validated HPLC methods. The similarity factor was calculated, taking into consideration as reference profile the mean in vitro dissolution data of Glucovance. The formulation process was undertaken using a reproducible DoE generated model, attained by the variation of each of the formulation factors on two levels, followed by the filling of the data resulted from the analytical testing of the tablets.

The model was fitted using Partial Least Squares method. For the assessment of the level of fitting, Q2, R2 and Anova tests were performed. The desired drug release pattern can be achieved by using a proper percent of superdesintegrant, by reducing the filler and by the presence of extragranulary added binder.

The results have shown that the experimental responses match the statistical generated model and that the investigation is reproducible.