374851 Fluid Bed Granulation: Towards a Comprehensive Process Model

Thursday, November 20, 2014: 9:30 AM
202 (Hilton Atlanta)
Robert Claudius Schardmüller1, Markus Pieber1, Gregor Toschkoff2, Simon D. Fraser1, Daniela Steigmiller3, Bruno Chilian3, Alfred Fetscher3, Martin Maus3, Michael Braun3, Sean Bermingham4, Johannes G. Khinast5 and Pavol Rajniak2, (1)Research Center Pharmaceutical Engineering (RCPE), Graz, Austria, (2)Research Center Pharmaceutical Engineering, Graz, Austria, (3)Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany, (4)Process Systems Enterprise Limited, London, England, (5)Institute for Process and Particle Engineering, Graz University of Technology, Graz, Austria

Although fluidised bed granulation (FBG) is a widely-used unit operation, its practical application is often guided by empirical methods and the experience of the operating staff rather than by systematic and scientifically-based strategies. Employed in various branches of industry (for producing fertilisers, detergents, industrial and agricultural chemicals, food products, and also pharmaceuticals), granulation in general - and fluid bed granulation in particular - remained more of “an art than a science” [1].

As also demonstrated in other areas, the development of realistic mathematical models that are interlinked with high-precision in-line process measurements can yield powerful tools for a knowledge-based control of process and product quality for all particulate processes [2]. The complex interplay of many different variables and processes during fluid-bed granulation poses a significant challenge in developing such models. The associated effects may be grouped into one of three categories [3]: wetting and nucleation, consolidation and growth, as well as breakage and attrition. Every realistic model for a fluid bed granulator must incorporate these three effetcs. In addition, the model needs to account for all process-relevant parameters (e.g., air and liquid flow rates, binder properties, etc.) that influence the sub-processes as model input.

Figure 1: Schematic of the process modelling approach (“flowsheeting”) using the custom fluid bed agglomerator unit.

In our work, we develop a model of the fluid bed granulator based on a basic model provided in the process simulation software gSOLIDS 3.1 (Process Systems Enterprise Ltd., London, UK). The basic model already contains agglomeration, drying, and elutriation of particles as separate phenomena. To make it suitable for batch processes, the extended model additionally takes into account the breakage of granulates, as well as the continuous introduction of spray. For breakage, different commonly used models are compared with respect to their applicability. The spray introduction is based on a new user-defined phenomenon for the wetting of particles. In addition, we also explored the possibility of introducing a liquid binder component as a part of an additional solid phase. We present results for the different approaches for wetting and for a selection of combinations of agglomeration and breakage kernels. The results are further compared to in-line measurements of particle size and moisture from industrial fluid bed processes of different scales.


[1]         J. D. Litster, Powder Technol. 130, 35 (2003).

[2]         I. T. Cameron, F. Y. Wang, C. D. Immanuel, and F. Stepanek, Chem. Eng. Sci. 60, 3723 (2005).

[3]         S. M. Iveson, J. D. Litster, K. Hapgood, and B. J. Ennis, Powder Technol. 117, 3 (2001).


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