The purpose of this study was to evaluate the influences of intrinsic drug mechanical properties and different granulation binder delivery processes on the physical and mechanical properties of high drug load granulations after wet granulation. Formulations (80% w/w) of acetaminophen (APAP), metformin and aspirin, which are brittle, viscoelastic, and ductile, respectively; were granulated by high-shear wet granulation. Two modes of binder delivery for wet granulation, either conventional or binder foam, were investigated. Particle size, surface area and pore size of the granulations were characterized. Compacts were prepared at a solid fraction of 0.9 under tri-axial decompression and Hiestand indices (worst-case bonding index (BIw) and brittle fracture index (BFI)) of the compacts were determined. APAP formulations exhibited the smallest geometric mean particle sizes (d(g)) and showed only slight differences in d(g) Values between the two granulation processes. Binder delivery mode affected mechanical properties of the granulated model drugs differently. Foam granulation appeared to enhance the granule plasticity for APAP while aspirin showed a mixed deformation mechanism based oil both its high BIw and high BFI values. The higher BIw value for aspirin after foam granulation may be attributed to improved binder distribution among particles during granulation. On the other hand, conventional wet granulation improved the plasticity of metformin as measured by the higher BIw and lower BFI values. Therefore, conventional wet granulation process conferred advantages in manufacturability and product quality for metformin; as compared to foam granulation which did not enhance plasticity for metformin. Based on this study, a wet granulation process can be selected based on knowledge of the intrinsic drug mechanical properties. (C) 2009 Elsevier B.V. All rights reserved.