Design space determination and process optimization in at-scale continuous twin screw wet granulation

Abstract At-scale industrial continuous twin screw wet granulation process was analyzed and optimized via design of experiment (DoE). The Box-Behnken method was selected to investigate the influence of key process variables on granule properties and tablet properties. The effects of the key process variables were analyzed. The experimental results have demonstrated that both the granule properties and tablet properties are influenced by the throughput, the screw speed and the screw element. Particularly, the screw element type and the milling process were found having significant effects on tablet tensile strength and disintegration time. The design space (DS) based on volume average granule diameter (Y 4 8