Conventional wet granulation is commonly used in the pharmaceutical industry for size enlargement, where small primary particles are binded together using agitation and a liquid binder. However, after the wet mass is produced, it needs to dry the granules for long periods of time causing high-energy inputs. This report presents a novel supercritical fluid CO2 granulator (SFG) to produce granule batches with low particle size distribution (PSD), while using less drying time and minimizing the additional drying steps. This study focused on understanding the effect of mixing (e.g., flow rate, location of inlet flow, agitation) and composition (e.g., binder and solvent type water vs. ethanol) in the SFG process. Sieves were used to measure the PSD, and scanning electron microscopy (SEM) was performed to observe the granules' shape. The PSD and the shape of the granules were used to evaluate the efficiency of the SFG process. The excipients used included anhydrous lactose and monohydrate lactose, while acetaminophen was used as the active pharmaceutical ingredient (API). The results show that the SFG process could effectively be used as an alternative to the conventional wet granulation process (Patent Pending # 62/398,645). The study also discusses how changes in the mixing and composition conditions affect the resulting granule size, distribution, and shape. Published by Elsevier B.V.