Identification of continuous twin-screw melt granulation mechanisms for different screw configurations, process settings and formulation

Abstract

Twin-screw melt granulation (TSMG) is a promising continuous manufacturing technology for the processing of high drug load formulations and to formulate heat- and moisture-sensitive active pharmaceutical ingredients (APIs). This study evaluates the influence of process parameters for TSMG, mainly focusing on the effect of the screw configuration combined with screw speed, throughput and barrel temperature, to elucidate the melt granulation mechanisms. For the kneading zone, the stagger angle was varied between 30°, 60° and 90°, and investigated for both the forward and the reversed direction. In addition to the process parameters, the influence of the formulation differing in their API-binder miscibility was evaluated. As responses, the granule (size, friability and porosity) and process properties such as torque were evaluated, indicating that the screw configuration is the most influential factor. Nucleation, consolidation and breakage are the granulation mechanisms for the forward and the neutral configuration, while consolidation and densification with shear elongation are identified for the reversed configuration. The formulations differ mainly in the forward and neutral configuration since the immiscible formulation shows a bimodal granule size distribution with a larger fraction of fines and weaker granules is obtained. For the reversed configuration, similar granulation mechanisms are seen for both formulations.