The aim of this study was to develop novel hydrogel-based beads and characterize their potential to deliver and release a drug exhibiting pH-dependent solubility into distal parts of gastrointestinal (GI) tract. Oxycellulose beads containing diclofenac sodium as a model drug were prepared by the ionotropic external gelation technique using calcium chloride solution as the cross-linking medium. Resulting beads were characterized in terms of particle shape and size, encapsulation efficacy, swelling ability and in vitro drug release. Also, potential drug-polymer interactions were evaluated using Fourier transform infrared spectroscopy. The particle size was found to be 0.92-0.96 mm for inactive (oxycellulose only) and 1.47-1.60 mm for active (oxycellulose-diclofenac sodium) beads, respectively. In all cases, the sphericity factor was between 0.70 and 0.81 with higher values observed for samples containing higher polymer and drug concentrations. The swelling of inactive beads was found to be strongly influenced by the pH and composition (i.e. Na(+) concentration) of the selected media (simulated gastric fluid vs. phosphate buffer pH 6.8). The encapsulation efficiency of the prepared particles ranged from 58% to 65%. Results of dissolution tests showed that the drug loading inside of the particles influenced the rate of its release. In general, prepared particles were able to release the drug within 12-16 h after a lag time of 4 h. Fickian diffusion was found as the predominant drug release mechanism. Thus, this novel particulate system showed a good potential to deliver drugs specifically to the distal parts of the human GI tract.