(303d) Characterization of Distributive Mixing Elements and Effect of Downstream Conveying Elements in Twin Screw Granulation

Twin screw granulation (TSG) is rapidly gaining interest from the pharmaceutical industry because of the flexibility in equipment design, ability to vary throughput and short product residence times. In TSG, the screw design and configuration strongly influences granule properties. This paper presents mechanistic studies performed on a Thermo-Fisher 16 mm granulator to elucidate the granule growth mechanisms for different configurations with kneading elements (KEs) and distributive mixing elements (DMEs), and downstream conveying elements in the extended setups. Measured granule properties were granule size distribution (GSD), shape, percent porosity, and liquid distribution (LD).

Granulation rate processes were studied in the distributive mixing elements (DME) of a twin screw granulator through characterization of resulting granule attributes. The screw configuration was varied by changing the orientation (forward versus reverse) and the placement of the elements (adjacent versus spaced). A model placebo formulation was used in the study. Regardless of the screw configuration, DME generated granules through breakage of large wet agglomerates from the conveying section and layering of un-granulated fines. The reverse orientation produced superior granule size distribution with improved liquid distribution attributes compared to the forward orientation.

To elucidate the effect of downstream conveying elements (CEs) on granule attributes, experiments were performed using three different screw lengths of the TSG. For each length of the screw, three different screw configurations were used: CE only and CEs in combination with 3 or 7 KEs. In the KE configured design, KEs were used with a 90º advance angle between successive KEs. At low liquid to solid ratio (L/S) values, the GSDs obtained for the three different screw lengths are similar (within experimental error). At high L/S values breakage of lumps (larger than 3mm) and layering of fines were observed with the addition downstream CEs. Addition of some downstream CEs resulted in improved GSD and LD, while further addition of downstream CEs gave similar GSDs within experimental error. This indicates that breakage and layering occur quickly and there is an optimal length of downstream CEs. LD results support these hypotheses as LD improves (with more liquid in fines and less liquid in lumps) with the addition of some CEs but becomes worse upon the addition of further downstream CEs.