Purpose <p>Granulation is one of the important unit operations in the manufacturing of solid dosage forms like tablets and capsules that regulate the quality of end products. It is a process of particle enlargement by agglomeration technique, which improves flow properties, compressibility, reduction of dust formation, drug content uniformity, dissolution rates, and overall product stability. Traditionally, it has been a batch process due to a better understanding of the process. However, there has been a shift towards continuous manufacturing using a Twin-screw granulator, which is more robust, scalable, and versatile for a wide range of applications.</p> Methods <p>This work presents the innovative use of Twin screw wet granulation (TSWG) in the development of Quetiapine fumarate (QTF) immediate release tablets. Various process parameters (Screw configuration, liquid-to-solid (L/S) ratios), and binders (HPC and PVP) were evaluated to determine their effect on granule quality. Further, the obtained granules were tested for particle size distribution and flow properties.</p> Results <p>A higher percentage of uniform-sized granules were yielded with three mixing zones even with a lower liquid addition compared to that of one mixing zone with a higher liquid addition. These granules were further tableted and tested for their hardness, friability, disintegration, and dissolution. The tablets disintegrated and released the drug (~ 95%) rapidly within 5&#xa0;min in 0.1 N HCl due to QTF’s high solubility and porosity of granules.</p> Conclusions <p>Overall, the understanding of process parameters and their influence on granule and tablet characteristics would help establish a more robust and continuous manufacturing of dosage forms.</p> Graphical Abstract <p></p>