Influence of the process parameters on the characteristics of starch based hot stage extrudates.

The influence of the process parameters on the characteristics of matrix formulations produced by means of hot stage extrusion was investigated using three experimental designs. The first one was designed to evaluate the importance of the screw speed (150-450 rpm) and the feed rate (2-12 kg/h), while the second and the third were designed to study the importance of the temperature profile (60-120 degrees C). The extrudates were produced with a laboratory twin screw extruder equipped with a 3-mm cylindrical die. The formulations consisted of 53% corn starch, 15% sorbitol, 2% glyceryl monostearate and 30% theophylline monohydrate as the model drug. The extrudates were characterized by Karl-Fischer titration, Hg-porosimetry, four-point bending and dissolution testing. From the first design it was concluded that the screw speed and feed rate hardly affected the water content of the extrudates, but that there was a clear influence on the extrudate radius, porosity, mechanical strength and dissolution behaviour. High screw speed-high feed rate processes in comparison with low screw speed-low feed rate processes caused an increase in extrudate radius and porosity and a decrease in mechanical strength and drug release rate from the matrix. It was clear that the contribution of the feed rate was higher than that of the screw speed. Expansion, promoted under certain extrusion conditions, could explain the obtained results. The second and third design revealed that only the maximum barrel temperature and not the whole temperature profile was responsible for the temperature effects on the extrudate characteristics. It was concluded that the maximum barrel temperature was the most critical parameter of the hot stage extrusion process.