Optimization of fluid bed formulations of metoprolol granules and tablets using an experimental design

The granulation process of a metoprolol tartrate (very difficult to process active pharmaceutical ingredient) formulation in laboratory scale fluid bed equipment was studied.

To study the influence of two formulation factors and three process parameters on the characteristics of the granules and subsequently of the tablets, in the case of fluid bed granulating of a powder mix containing metoprolol tartrate.

In order to study the influence of formulation factors (binder solution concentration and the silicon dioxide ratio) and process factors (atomizing pressure, the length of the final drying phase, and the inlet air temperature) on the technological and pharmaceutical properties of granules and tablets, a fractional factorial experimental design resolution V+ with five factors and two levels was used.

A high atomizing pressure allows us to obtain fine granules with large poly-dispersion index and granules with high tapped and untapped density, tablets with short disintegration time, short mean dissolution time, and a high percentage metoprolol tartrate release in the first 15 minutes. A lower concentration of binder solution allows us to obtain granules with very good flow properties, tablets which have no tendency to stick on the set punch of tabletting machine and no capping. The final drying time of granules has an influence only on the granule's relative humidity and tapped and untapped density, without any influence on the granules flow properties.

The practical experimental results from the formulation processed in optimal working conditions were close to the predicted ones by Modde 6.0 software.