Technical Report 56, c4e-Preprint Series, Cambridge
Applying response surface methodology to multidimensional granulation modelling
ref: Technical Report 56, c4e-Preprint Series, Cambridge
Associated Theme: Particle Processes
A new multidimensional model for the wet granulation of powders is presented, which includes the transformations coalescence, compaction, reaction, penetration and breakage. The particles and their composition are described by six dimensions. The particle model consists of two kinds of solid (original and reacted), pore volume, two kinds of liquid (on the external surface and in the pores) and the number of entities (beads) in the particle. This allows for a detailed tracking of the granulation process. Process operating conditions such as the impeller speed of the mixer and the binder composition are reflected in the descriptions of the transformations. The model framework is tested against experimental results (Simmons, Turton and Mort. Proceedings of Fifth World Congress on Particle Technology, paper 9d, 2006) from granulation of sugar particles with different PEG based binders in a bench scale mixer. The experiments were carried out for different impeller speeds, binder compositions and process durations. A response surface approach is chosen in order to establish important model parameters of the subprocesses incorporated in the model through an optimisation step, fitting the model to the set of experiments. These model parameters are the collision rate constant, the compaction rate constant, breakage rate constant, and the reaction rate constant. The simulations with this set of parameters show that the model predicts the correct trends, not only in time, but also for crucial process conditions such as the impeller speed and the binder composition. The influence of their choice is discussed for the porosity of the particle ensemble that is linked to important macro properties like the dissolution behaviour and bulk density. Furthermore, statistics of the different events such as collisions, coalescence and breakage reveal which processes are governing the granulation at different stages under varying conditions. For instance, it has been found that successful coalescence events outnumber the breakage events by a factor of up to three for low impeller speeds.
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