Oscillatory rheometry tests carried out on chitosan/glutaraldehyde dispersions provide information useful to select the optimum conditions for the cross-linking process during bead preparation. An amount of cross-linker enough to react with 70–75% of the chitosan amino groups is adequate to prepare consistent but yet flexible beads with pH-sensitive swelling. The temperatures at which the beads are obtained and dried are also key factors in the performance of the beads owing to their influence on the kinetics and final degree of cross-linking. Dried beads synthesised at 37 °C exhibited faster swelling rates than the ones prepared at 20 °C and, even, disintegrated after 30 min in 0.2 M acetic acid. The amount of metronidazole loaded strongly depends on the composition of the medium and the thermal-hydration history of the beads. Better results were obtained with 0.2 M acetic acid > 0.1 M HCl > purified water > pH 7.5 buffer phosphate, and with freshly prepared swollen beads > dried beads > rehydrated dried beads. These results highlight the importance of considering both the inherent and the external factors that influence the degree of swelling in order to optimise the loading capacity of chitosan beads, which can be obtained by a simple procedure and are able to release the whole dose in less than 30 min in an acidic environment.