Comparison of scale-up strategies in twin-screw wet granulation

The aim of this study was to compare different scale-up strategies in twin-screw wet granulation and investigate the impact of the selected strategy on granule and tablet properties for a defined formulation. For the scale-up, a granulation process was transferred from a QbCon® 1 with a screw diameter of 16 mm to a QbCon® 25 line with a screw diameter of 25 mm. Three different scale-up strategies were introduced based on differences in process parameters and their resulting effects on various aspects. such as the powder feed number as a surrogate for the barrel fill level or the circumferential speed. Both are highly dependent on screw diameter and screw speed (SS), while the barrel fill level also depends on the overall throughput.

Granules produced on the larger scale were significantly larger due to the larger gap size in the granulator, however, these differences were eliminated after milling. Despite major differences in powder feed number, circumferential speed, overall throughput and SS, product properties for both tablets and granules were strikingly similar after milling on both scales and with all applied strategies. For the selected formulation the effect of varying liquid to solid ratio at the same scale was much higher than the differences between scale-up strategies. The results of this study are promising for future process scale-up from lab scale to production scale in twin-screw wet granulation, as they are indicating towards a robust granulation process leading to similar tablet properties afterwards.

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Materials

Experiments on both scales were performed using the formulation described in Table 1. Mannitol (MAN 160C, Pearlitol® 160c, Roquette Pharma, France), microcrystalline cellulose (MCC, Vivapur 101, JRS Pharma, Germany) and povidone K25 (PVP, Kollidon 25, BASF, Germany) were used in the preblend for granulation. To prepare the final blend for tableting, mannitol (w/w) (MAN M200, Parteck M200, Merck Millipore, Germany), croscarmellose-sodium (CCS, Ac-Di-Sol®, FMC BioPolymer, Germany)

Marcel Franke, Thomas Riedel, Robin Meier, Carsten Schmidt, Peter Kleinebudde, Comparison of scale-up strategies in twin-screw wet granulation, International Journal of Pharmaceutics, Volume 641, 2023, 123052, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2023.123052.

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