Comparison between twin-screw and high-shear granulation - The effect of filler and active pharmaceutical ingredient on the granule and tablet properties

The aim of the study was to compare continuous twin-screw granulation (TSG) with batch-wise high-shear granulation (HSG). Two different formulations containing either microcrystalline cellulose (MCC) and mannitol or MCC and dibasic calcium phosphate (DCP) as fillers were used. Three different active pharmaceutical ingredients (APIs) (allopurinol, paracetamol and metformin HCI) were used as model substances. To find the suitable liquid-to-solid (L/S) ratio for the granulations, preliminary trials were carried out using a mixer torque rheometry (MIR). Both granule and tablet properties were studied. Granules were characterized with respect to particle size distribution and flowability, while tablets were analysed for tensile strength. Both granulation techniques produced granules with unimodal particle size distribution after milling with the selected L/S ratios. Continuous TSG was less sensitive for liquid amount than HSG when comparing the granule size and tensile strength of tablets. The tabletability of the MCC-DCP formulation was decreased after the wet granulation, whereas the tabletability of MCC-mannitol was increased after wet granulation. Tablets made of TSG granules had a higher tensile strength than HSG tablets for all formulations. Even the APIs with poor compaction properties produced tablets with sufficient tensile strength. All the model substances behaved in a same way independently of the particle size and solubility of the pure API. These findings confirmed that continuous twin-screw granulation is a good alternative to batch-wise high-shear granulation. (C) 2020 Elsevier B.V. All rights reserved.