A work has been done to study the individual and interacting effects of formulation variables, using a 23 fractional factorial design. The effects of five variables, namely, relative density of tablets, nature and concentration of binder, compression process, and compression speed on the tensile strength and percent survival of Bacillus subtilis spores in Diclofenac tablet formulations were determined. The effects of these variables were studied both singly and when they interact with each other in two fractional designs (Woolfall, 1964). The first fraction comprised of Nature (N) and Concentration (C) of binder, and Relative density of tablets (D) while in the second fraction, Compression speed (S), Compression process (P) and Relative density of tablets (D) were studied. In the first fraction, concentration of binder had the highest effect on tensile strength with the ranking C > D > N for both DCS (formulation containing Corn starch) and DDCP (formulation containing DCP), and C > N > D for DL (formulation containing Lactose). On the percent survival of Bacillus subtilis, relative density of tablets showed the highest effect with the ranking D > C > N for both DCS and DL, and D > N > C for DDCP. In the second fraction, compression speed generally had a great effect on both tensile strength and percent survival in all the formulations. The results of interactions among the variables showed the highest effect on tensile strength from interaction between concentration of binder and relative density of tablets (C-D) while interaction between compression speed and relative density of tablets (S-D) had the highest effect on percent survival in all the formulations. A fractional factorial design proved suitable in determining the magnitude of both the individual and interacting effects of the variables. The study showed that each of these variables has to be properly considered in producing tablets of satisfactory strength and reduced microbial survival.