This work was aimed at the use of dissolution testing and similarity factor to assess the level of damage taken by active drug microspheres during compression in tablet dosage form. To achieve that, combinations of suitable excipients were used to protect drug microspheres during compression. The excipients were used in the form of powders, granules or placebo pellets prepared by extrusion-spheronization technology. The excipients were evaluated alone, in combinations and post-compression into compacts. Preliminary experiments included assessing density, hardness, friability and disintegration of all the selected excipients. Based on such experiments it was found that the flowability of combination of powders was more acceptable than individual excipients. Two combinations of microcrystalline -starch and microcrystalline cellulose -calcium carbonate granules were selected to be compressed with pellets of the active pharmaceutical ingredient ketoprofen. In all the combinations used there was a significant amount of damage to drug pellets. The kinetics of drug release appears to follow the zero-order rate, which remained unchanged even when a significant degree of damage to pellets occurs. It was found that a high level of excipients is required in order to prepare microspheres as a rapid disintegrating tablet.