Effect of primary particle size on granule growth and endpoint determination in high-shear wet granulation

Abstract

The effect of primary particle size on granule growth and endpoint determination during high-shear wet granulation was investigated. Three different grades of lactose monohydrate, having different volume mean particle sizes (39, 84, and 127 μm), were granulated with water in a 25-l high-shear mixer. Increasing primary particle size results in larger, less porous wet granules. This is consistent with the expectation that both the capillary and viscous interparticle forces decrease with increasing primary particle size, and the resulting granules become more deformable. Increasing the volume of granulating liquid reduces the porosity, but has only a minor influence on wet granule size. In contrast, the apparent dry granule size increases markedly with increasing granulating liquid. Changes in the impeller torque correlated reasonably well with changes in the wet granule size distribution, although torque is not a state function of wet granule size. It is also influenced by primary particle size and the chaotic nature of wall build-up and collapse. Impeller torque correlated poorly with apparent dry granule size. This is because of the changing nature of interparticle forces upon drying. Thus, understanding the relationship between impeller torque and dry granule size requires understanding both wet and dry granule interparticle forces and how they are influenced by pore saturation and primary particle size. One needs to be keenly aware of these limitations if using impeller torque to determine granulation endpoint.