Sustained-release diclofenac potassium orally disintegrating tablet (ODT) formulations have been prepared and investigated. The ODTs were prepared by incorporating diclofenac potassium (DP), as a model for negatively ionizable drugs, in microcapsules that were prepared by the solvent evaporation method from a mixture of DP and different ratios of Eudragit RS and Eudragit RL, which are positively ionized synthetic polymers. The ODTs were prepared by direct compression of mixtures containing microcapsule formula M4, crospovidone as a super-disintegrant and water soluble excipients (mannitol or lactose and sorbitol). Diclofenac potassium ODT F2, showed acceptable hardness (4.08 KP) slight friability (2.13 %) and disintegration time of 22.41 s with a sustained drug release profile. Microcapsule characterization (DSC and FT-IR) and dissolution behavior suggests the presence of specific interaction between the carboxylate group of diclofenac and the quaternary ammonium group in the polymers.