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

The effect of primary particle size on granule growth and endpoint determin ation during high-shear wet granulation was investigated. Three different g rades of lactose monohydrate, having different volume mean particle sizes ( 39, 84, and 127 mu m), were granulated with water in a 25-I high-sheer mixe r. Increasing primary particle size results in larger, less porous wet gran ules. This is consistent with the expectation that both the capillary and v iscous interparticle forces decrease with increasing primacy particle size, and the resulting granules become more deformable. Increasing the volume o f granulating liquid reduces the porosity, but has only a minor influence o n wet granule size. In contrast, the apparent dry granule size increases ma rkedly with increasing granulating liquid. Changes in the impeller torque c orrelated reasonably well with changes in the wet granule size distribution , although torque is not a state function of wet granule size. It is also i nfluenced by primary particle size and the chaotic nature of wall build-up and collapse. Impeller torque correlated poorly with apparent dry granule s ize. This is because of the changing nature of interparticle forces upon dr ying. 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 t orque to determine granulation endpoint. (C) 2000 Elsevier Science S.A. All rights reserved.