Development of a process map: A step towards a regime map for steady-state high shear wet twin screw granulation

Abstract

Twin-screw granulation is an emerging continuous granulation technique in the pharmaceutical industry. The flexibility in process settings such as the binder addition method (wet vs. dry), screw configuration, screw speed and material throughput allows to modify the granule size and shape. However, twin-screw granulation, being a rather new granulation technique, is not yet as well understood as batch-wise high shear wet granulation. Furthermore, most of the studies performed on twin-screw granulation are limited to a certain design and scale of the twin-screw granulator. In this study, in order to improve the understanding about the granulation process and to comprehend the applicability and limits of the process variables in a scale independent manner, the regime theory was applied to one specific twin-screw granulator equipment. In this study, α-lactose monohydrate was granulated with polyvinylpyrrolidone (2.5%, w/w) as binder. The screw configuration of the 25mm diameter co-rotating twin-screw granulator from the ConsiGma-25 unit consisted of one or two kneading zones of six kneading elements each (1×6 and 2×6, respectively), at a stagger angle of 60°. The specific mechanical energy, which involves the combination of screw speed, material throughput and torque required to rotate the screws was correlated with the applied liquid-to-solid ratio to present process maps. The study suggested that, despite an increase in the granule size by the increasing liquid-to-solid ratio, most of the liquid contributes to formation of oversized granules. Therefore, keeping the liquid-to-solid ratio in a lower range and increasing the energy input to the system can be effectively used to lower the mean granule size. Changes in the screw geometry should also be explored to improve solid liquid mixing and breakage of oversized granules to narrow the width of the size distribution. Since, such a process map is limited to a selected formulation and equipment design, process maps based on several formulations and mechanistic mathematical modelling tools should be applied to identify the mechanisms and relevant dimensionless groups that control granule attributes, with the ultimate aim of producing a generalised regime map.