(226b) Population Balance Modeling of Twin Screw Wet Granulation: Effect of Screw Length on Granule Attributes

Twin screw granulation (TSG) is rapidly gaining interest from the pharmaceutical industry due to its flexibility in equipment design, wide range of throughputs and short product residence times. Screw design and configuration are of key importance in TSG because of their strong effects on granule attributes. This paper presents mechanistic studies performed on a Thermo-Fisher 16 mm granulator to elucidate the effect of downstream conveying element (CE) section for three different configurations namely, CE only and CE combined with three and seven kneading elements (KE) with 90-degree advance angle. Three different screw lengths of the TSG were used for each screw configuration. Measured granule properties were granule size distribution (GSD), percent porosity, and liquid distribution (LD). At low liquid to solid ratio (L/S) values, similar GSDs were obtained for the three different screw lengths (within experimental error). At high L/S values however, 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 suggests 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.

A two dimensional, compartment based population balance is developed to predict granulation behavior in the extended screw configuration. We use the framework developed by Barrasso et al. and experimental data and mechanistic understanding studied at Purdue University as the basis for developing the model, and particularly the rate expressions for nucleation and breakage, which dominate the development of granule attributes in the TSG. Based on this mechanistic approach, utilizing the regime-separated nature of the TSG, the granulation process is modeled as a series of compartments, where each screw element type represents one compartment in which the mechanisms are clearly established. The element characterization data allows the fitting of the breakage rate constants and other rate parameters on an element by element basis. The combined model for the whole screw length can then be used to track the evolution of granule properties from any combination of elements. Model results are compared with experimental results for both size and liquid distribution, and the usefulness of the model as a design tool is critically evaluated.