The evaluation of drug substances and pharmaceutical excipients for their physico-mechanical properties is of prime importance in the development of oral solid dosage forms. Some of these materials are brittle and consolidate by brittle fracture or fragmentation, some others are ductile and consolidate by plastic deformation, while others consolidate by both fragmentation and plastic flow. One method of characterization is by determination of Hiestand's Indices of Tableting Performance (ITP), Bonding Index, Brittle Fracture Index and Strain Index, from measurements of indentation hardness (P) and tensile strengths of large compacts with a hole (sigma(TO)) and without a hole in the center (sigma(T)). Three individual fractional factorial designs have been employed for identifying experimental conditions that would maximize the differentiation between materials in terms of their ITP. Factors that are varied in the factorial designs include compact size, compact weight, compression pressure, indenter diameter, indenter release angle, storage temperature, storage time, strain rate during tensile break. Microcrystalline cellulose and acetaminophen were chosen as representatives of highly and poorly compatible materials, respectively. Factor levels were chosen to span the practical limitations of the experiments. The Strain Index analysis indicates that the four main effects, indenter release angle, indenter diameter, storage temperature and compression pressure, and seven two-factor interactions, three of which involve the material characteristics, are significant. The Brittle Fracture Index analysis indicates three main effects, material, compact size and storage time, and five two-factor interactions, two of which involve the material properties, are significant. The analysis with porosity as a covariate makes no substantial reduction in the factors which influence the indices. Additional experiments are required to deconfound the major effects, especially the 'material' effect.