The role of the screw profile on granular structure and mixing efficiency of a high-dose hydrophobic drug formulation during twin screw wet granulation.

This study aimed at systematically investigating the role of distributive comb mixing element (GLC) and neutral dispersive mixing kneading block element (K90) on the structure and physical properties of granules containing high-dose of poorly water-soluble drug. Albendazole was used as the model drug at 50 wt% drug loading. Lactose monohydrate and microcrystalline cellulose were used as diluent, and 3 w/v% hydroxypropyl cellulose aqueous solution was used as binder liquid. It was found that the use of GLC element resulted in formation of granules with higher internal porosity, more homogeneous binder distribution, smaller particle size, superior compaction properties and tabletability while K90 kneading element produced relatively larger and denser granules with less homogeneous binder distribution where binder was mainly concentrated in larger granules. The use of downstream GLC element was shown to result in an approximately 8% and 57% reduction in the D50 for 0.2 and 0.3 liquid-to-solid ratios, demonstrating a significantly higher sensitivity of granule size to screw profile at higher liquid-to-solid ratios. The axial mixing efficiency was assessed by measuring the residence time distribution of the granulation process with screw profiles containing K90 and GLC elements. It was found that granules had longer mean residence time and broader residence time distribution within GLC element due to enhanced backmixing and axial dispersion processes. The continuous "fragmentation-reagglomeration" cycle was proposed to be the main advantage of distributive GLC element in granulation of hydrophobic powders.