Comparison of granules obtained with two twin-screw granulators of different diameter working at the same shear rate

Abstract

We study the response of two twin-screw granulators of different barrel diameter to the variation of three process parameters (liquid-to-solid ratio, screw speed and throughput), while maintaining the same shear rate field along the screws. Various responses, including size distribution, porosity and content uniformity, were measured to determine granule characteristics. The set of experiments was based on a central composite design face-centered. Granules in both systems showed drug content consistent with expected values across varying process parameters. Relative granules size, normalized with the granulator gap, was larger for the equipment with the smaller gap. The liquid-to-solid ratio (LSR) was the most influential parameter affecting the granule size. Specifically, dimensional granule size increased with LSR values in both systems, consistent with previous studies. Elevated LSR values resulted in greater amounts of over-granulated material, whereas lower values produced exceedingly small (fines) or under-granulated material. The minimum amounts of both over- and undergranulated material were found at intermediate LSR values. Porosity varied differently between the systems, with a consistent reduction observed as LSR decreased from 0.3 to 0.4. Optimization studies revealed that central values of LSR and screw speed minimized fines and bigger granules while maximizing porosity, critical attributes for downstream processing. Granule size and porosity exhibited no significant correlation with tablet tensile strength across both systems. These findings offer valuable insights for optimizing pharmaceutical manufacturing processes to enhance product quality.