(47c) Experimental Study of Wet Granulation in Fluidized Bed: Impact of the Binder Properties on the Granule Morphology

Purpose: To investigate impact of the physical properties of the hydroxypropyl-cellulose (HPC) binder solution on the growth and the mechanical and morphological properties of the manitol SD-200 granules produced in the fluidized bed. Methods: First, the particle size distribution (PSD) analysis of the manitol particles was performed together with the detailed analysis of morphological properties (mean gyration radius, aspect ratio, surface roughness) based on the Scanning Electron Microscopy (SEM) images [ 1 ]. Second, the viscosity, density, surface tension, size of the spray droplets, wetting characteristics on the manitol of the (HPC + water) solutions with different HPC concentration were determined. Third, three wet granulation experiments were done each with binder solution of different HPC concentrations in a pilot plant fluid-bed granulator. The manitol : HPC ratio was kept constant and the hydrodynamic conditions were kept as similar as possible in all experiments. The flowrate of the fluidizing air was gradually increased during experiments to maintain good and consistent fluidization pattern. Product samples were taken during the experimental runs and used for the PSD evaluation. Finally, the mechanical and morphological properties of the produced granules were measured and correlated to the HPC concentration of the binder used in the experiments. A simple physically-based criterion [ 2 ] was also evaluated, which employs the morphological properties of manitol (size and surface roughness) together with physical properties of the used binder for prediction of the coating vs. agglomeration regime at given flow conditions (collision velocity). Results: The binder-solution viscosity, equilibrium wetting angle and droplet size increased greatly with the HPC concentration in the range of 5 ? 30% of HPC. On the other hand, the surface tension of different binders remained almost constant. The observed granule growth for different binder concentrations is a strong function of the binder concentration. A significant ?coating? period followed by a slow granule growth was observed for the case with the diluted 5% binder. The ?coating? period is significantly shorter for the 10% HPC binder and doesn't exist for the 15% HPC for which an immediate and fast granule growth was observed. A clear correlation between the granule porosity (evaluated by X-ray tomography) and the binder concentration was also found. These regimes and correlations are qualitatively predicted when the criterion for the Type I and II coalescence [ 2 ] was used in the model. Conclusions: Physical properties of the HPC binders with different concentration of the HPC have direct impact on the granule growth and granule properties. A simple physically based criterion was successfully used for prediction of different growth regimes. Clear correlations between the binder concentration and the granule properties were observed which can be used for optimization of desired granule properties.

References: [1] Stepanek, F., Rajniak, P., Chern, R., & Mancinelli, C.: Modeling of multi-component granule formation in a wet granulation process. WCPT 2006,section TWB16, Orlando. [2] Liu, L.X., Litster, J.D., Iveson, S.M., & Ennis, B.J.: Coalescence of deformable granules in wet granulation processes. AIChE J. 46 (2000) 529-539.