Effect of fill level in continuous twin-screw granulator: A combined experimental and simulation study

Twin-screw granulators for continuous wet granulation have attracted interest in the pharmaceutical industry. The physical properties of granules and tablets prepared through the twin granulation process depend on several factors, such as screw and barrel geometries, operating conditions, and formulations of raw materials. The fill level has been reported to be one of the most important factors in determining granule properties. However, the mechanism of the fill level effect on granule properties has not yet been fully clarified. In this study, the effects of the fill level in the twin-screw granulator on granule and tablet properties were investigated through a combination of experimental and simulation studies. In the experiment, temporal changes in the fill level were directly measured. It was found that a high fill level increased granule strength, resulting in large tablet hardness. The discrete element method simulations demonstrated that the compressive force on the particles in the granulator strongly depends on the fill level. In addition, by combining the experimental and simulation results, it was quantitatively revealed that a high fill level increased the interparticle adhesion, leading to the high hardness of tablets prepared with the granules.