(62d) Theoretical and Experimental Study of Wet Granulation in Fluidized Bed: Comparison of Experiments with Models of Different Complexity

Purpose: To compare mathematical models of different complexity with wet granulation experiments in fluidized bed granulators; evaluate the models by fitting to experimental data for different solid/binder systems at different operating conditions; discuss advantages/disadvantages of different models for simulation and scale-up of the pharmaceutical wet granulation processes. Methods: Fundamental investigation and modeling of wet granulation should capture and combine the following four key features of this complicated process: 1.Population balancing (PB) of growth and breakage of different granules; 2.Hydrodynamic modeling of the gas ? solid mixture flow using Computational Flow Dynamics (CFD); 3.Modeling of contact mechanics and granule formation; 4.Well controlled experimental study of the wet granulation. These particular features were studied independently in our recent works [1, 2, 3]. A methodology combining all four aspects for the analogous problem of attrition during pneumatic conveying was also reported [4]. Application of similar methodology to the wet granulation process is presented in this contribution. First, experimental results for different solid + binder systems were compared with homogeneous population balance models assuming different empirical and physically based agglomeration kernels. The homogeneous PBE models were solved using Quadrature Method of Moments (QMOM), which allows very fast solution and optimization of the agglomeration kernel parameters. Next, the rigorous models for homogeneous systems were solved using model parameters from the previous step. Finally, inhomogeneous CFD models (combining FLUENT granular model for modeling of gas-solid flow, QMOM for solution of PB, kinetic theory of granular flow for the number of collisions calculation and mesoscale modeling for the success factor evaluation) are employed and compared with experiments.Results: The simplest homogeneous models solved by QMOM allow very fast solution and parameter optimization and provide basic information about evolution of moments of particle size distribution. More detailed (but also more time consuming) rigorous methods for solution of the same homogeneous models allow computation of composition of different size classes (?sieve assay?). Generally, the homogeneous models can be recommended for prediction of the granulation process within the range of the tested operating conditions (interpolation). The kernel parameters of the homogeneous models can be used as good estimates for simulation with the most detailed and complex CFD models. Comparison of the homogeneous vs. CFD models indicate very good mixing in the fluidized bed granulators for the tested experimental systems. Authors believe, that the tested CFD models can also be used for extrapolation of the operating conditions and scale-up of the wet granulation process. References: [1] Rajniak, P., Fox, R., Dhanasekharan, K., Stepanek, F., Chern, R.: Solution of Population Balance Equations for Wet Granulation. 5-th World Congress on Particle Technology, Conference Proceedings, CD #2. 23-27 April 2006, Orlando. [2] Stepanek, F., Ramachandran R., Rajniak, P., Chern, R., & Mancinelli, C.: Modeling of Multi-component Granule Formation in a Wet Granulation Process. 5-th World Congress on Particle Technology, Conference Proceedings, CD #2. 23-27 April 2006, Orlando. [3] Rajniak, P., Mancinelli, C., Chern, R., Stepanek, F., Farber, L., Hill, B.: Experimental Study of Wet Granulation in Fluidized Bed: Impact of the Binder Properties on the Granule Morphology. 5-th World Congress on Particle Technology, Conference Proceedings, CD #2. 23-27 April 2006, Orlando. [4] Rajniak, P., Sinka, C., MacPhail, N., Chern, R., Fitzpatrick, S.: Modeling and Measurement of Granule Friability. 5-th World Congress on Particle Technology, Conference Proceedings, CD #2. 23-27 April 2006, Orlando.