Evaluation of Process Parameters for Continuous Manufacturing of Quetiapine Fumarate Immediate Release Tablets Using Twin Screw Wet Granulation.

PURPOSE

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.

METHODS

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.

RESULTS

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 min in 0.1 N HCl due to QTF's high solubility and porosity of granules.

CONCLUSIONS

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.