This paper proposes a simulation model which describes the formation of particulate network structure by particle settling, where agglomerate growth rate is strongly influenced by particle bridging stemming from dispersant as well as solid content. The network formation mechanism is essentially attributed to the collisions of dispersed particles and agglomerates in the initial dispersion, leading to a percolation network structure, in which the clusters are connected through the structure at the percolation threshold. It is demonstrated that two-dimensional model for settling of monodisperse particles satisfactorily expresses the dependency of network structure morphology on particle bridging, and enables us to understand the essentials of network formation mechanism qualitatively. Particle collisions in a slurry with a small solid fraction lead to particle aggregates and dendrite growth, resulting in network structure with directional change in packing fraction. The network structure formed in a concentrated slurry, on the other hand, shows the morphology with loose packing of clusters, and has no directional change in packing fraction.

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Network formation process by particle settling in binary dispersion is simulated, where the formation mechanism is essentially attributed to collisions of dispersed particles and hence the difference in their settling velocities. It is demonstrated that two-dimensional particle settling model satisfactorily expresses the dependency of network structure morphology on the mixing ratio in binary dispersion, and enables us to understand the essentials of network formation mechanism qualitatively. The packing fraction of network structure formed in binary dispersion is shown to be lower than that formed from monodisperse particles. The binary dispersion which results in the network structure with a minimum packing fraction contains a small number of large particles, and shows an indication of phase subsidence during the particle settling process, suggesting that the mixing ratio strongly influences the morphology of network structure. In the region where free settling of large particles is dominant, particle collisions lead to particle aggregates from the bottom and form dendrites. As the growth of aggregate becomes dominant, the network structure tends to show a morphology with loose packing of clusters. It is also shown that the network structure formed in binary dispersions with any mixing ratio has no directional change in packing fraction.

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The authors propose a new granulation technique employing a spray fluidized bed granulator that produces core particles with high drug content suitable for the film coating directly from slurry materials of poorly water-soluble drugs. Ethenzamide (ETZ) particles dispersed in a binder (hydroxypropylcellulose) solution were used as the model slurry material. In order to elucidate the granulation mechanisms of slurry materials in the granulator, the physical properties such as particle size distribution, compressive strength, circularity, specific surface area and bulk density of the granules produced under various binder concentrations and different fluidizing air velocities were measured. Coating of the granules produced from the slurry material was successively performed by using ethylcellulose-based Aquacoat in the granulator and the dissolution test was carried out to evaluate the granules as core particles. Experimental results showed that the granule growth mechanism was characterized by the following three processes: 1) generation of fine particles by spray drying, 2) agglomeration of fine particles, and 3) layering of fine particles onto the surface of individual agglomerates. It was found that spherical granule products with a high bulk density were obtained by the layering granulation and can be applied to core particles. The dissolution of EZT from the coated core particles was well controlled by changing the amount of coating agent. The granulation technique to produce core particles with a high drug content of EZT from its slurry was established using the direct granulation method with fluidized bed granulator.

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