Suppositories are formulated on weight basis on the assumption that the medication replaces a portion of the suppository base as a function of its density. The effects of drug concentration (C) and drug type (D) on the displacement factor (DF) of drugs in suppository bases (B) were investigated. Three drugs: paracetamol (PCM), sulphathiazole (STZ) and zinc oxide (ZNO), and two bases: polyethylene glycol (PEG) and shea butter (SB) modified with beeswax were studied. Densities of the drugs and bases were determined. Blank and medicated suppositories were prepared using fusion method and the quantity of base displaced by the drug determined. The densities of the drugs and their DF with respect to the two bases ranked ZNO >>> STZ > PCM. An optimum concentration for each drug was obtained beyond which the DF of the drug in the bases remained constant. The bulkier the drug, the smaller the concentration required to determine the displacement factor. No significant difference (P > 0.05) was found between the calculated density ratios of the drugs/suppository bases and their experimentally determined DF. Based on 23 factorial experimental design, the ranking of individual variable effects on the (DF) was D >> C >>> B, while interacting effects’ ranking was C-D >>> B-D > B-C. Depending on the bulkiness of the drug, it is suggested that drug concentrations between 10 and 25% w/w should be used for accurate determination of DF in the bases.