(641d) Fluid Bed Granulation: Towards a Comprehensive Process Model

Rajniak, P., Research Center Pharmaceutical Engineering
Toschkoff, G., Research Center Pharmaceutical Engineering
Pieber, M., RCPE
Fraser, S. D., Research Center Pharmaceutical Engineering (RCPE)
Braun, M., Boehringer Ingelheim Pharma GmbH & Co. KG
Steigmiller, D., Boehringer Ingelheim Pharma GmbH & Co. KG
Fetscher, A., Boehringer Ingelheim Pharma GmbH & Co. KG
Maus, M., Boehringer Ingelheim Pharma GmbH & Co. KG
Bermingham, S., Process Systems Enterprise Limited
Khinast, J. G., Graz University of Technology

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).