Distribution and accessibility of binder in wet granules

The effect of primary particle morphology on the spatial distribution of binder in wet granules was investigated by numerical simulations. The shape factors of four commonly used pharmaceutical excipients – mannitol, lactose, microcrystalline cellulose, and calcium phosphate – were evaluated by digital image analysis and used for three-dimensional computer reconstruction of virtual particle populations. The formation of wet agglomerates was simulated by close random packing of primary particles and then finding the equilibrium distribution of a liquid binder in the pore space within the close packed structures, using the Volume of Fluid (VOF) method. The spatial distribution of binder in the computer-generated wet agglomerates was then analysed and the dependence of the fractional surface coverage by liquid on the overall binder/solids ratio was systematically obtained for different values of primary particle surface roughness. The obtained dependence was used to explain experimentally observed differences in the granulation kinetics of the four pharmaceutical excipients under otherwise identical conditions.