Twin screw wet granulation: Influence of formulation parameters on granule properties and growth behavior

This study investigated the effect of formulation parameters on granule properties and growth behavior using a 16 mm twin screw granulator. A model placebo formulation composed of lactose (73.5%), microcrystalline cellulose (20%), hydroxypropylmethyl cellulose (5%) and croscarmellose sodium (1.5%) was used. Variation in the primary particle size was achieved by using three grades of lactose with unique particle size attributes. The incorporation of the binder in a dry versus liquid form was also examined. The granule formation and growth behavior of the different grades of lactose was investigated by varying the liquid to solid (L/S) ratio between 0.15 and 0.45 at 0.05 intervals. The twin screw granulator demonstrated an overall robustness towards remarkable changes in the formulation characteristics, where the three formulation grades displayed similar growth behavior at different L/S ratios. However, granule size analysis demonstrated a bimodal distribution for all formulation grades, with the presence of lumps and un-granulated fines even at the lowest liquid level. This indicated poor liquid distribution inside the granulator, particularly with the liquid addition in a dripping mode and the relatively short residence time available for mixing the different components. The addition of the binder in the liquid phase reduced the level of fines generated in comparison to using binder in the dry form. Granule porosity decreased with the increase in L/S ratio and percent binder in the liquid phase, indicating more consolidation. The results of this study highlight the need to improve liquid distribution within a twin screw granulator to optimize its utilization in a continuous manufacturing environment.

Changes in the granule size distribution of twin screw-granulated material with the increase in liquid to solid ratio.Figure optionsDownload as PowerPoint slideHighlights
► Robust performance of twin screw granulators to changes in formulation characteristics such as primary particle size and granulating liquid composition.
► Improvement in granule properties upon incorporation of the binder in the liquid phase.
► Broad granule size distribution at different liquid levels and formulation grades.
► The need for improving liquid distribution in twin screw granulators for better control over granule properties.