Norfloxacin is a fluorquinolone that can interfere with antacids that contain aluminum and magnesium salts by complexation and modification of its solubility, which reduces its absorption and may lead to therapeutic failures. The purpose of this work was to evaluate the effect of the pharmaceutical design on this interaction and to develop a formulation of norfloxacin tablets in which this process could be avoided. Norfloxacin tablets were designed in 28 formulations. The interaction was studied in terms of in vitro dissolution behavior (USP 23, apparatus 2) in simulated gastric fluid with different doses of four commercially available antacid preparations. It was observed that dissolution rates were markedly reduced in the presence of all antacids studied. This phenomenon was practically avoided with some formulations of norfloxacin tablets in which a disintegrant (sodium starch glycolate or crospovidone) was included. These results indicated that the chelation among metal ions and norfloxacin could be affected by the delivering ability of the drug in the tablet. It was demonstrated that the pharmacotechnical design could modify an interaction process. Some formulations of tablets, in which the reduced dissolution rates in the presence of nonsystemic antacids in vitro was practically avoided, were developed by direct compression.