A PMMA (polymethyl-methacrylate)–sorbitol-based capsule system was recently developed, and the permeability of 16 types of capsules with different wall thicknesses and sorbitol contents tested. By optimizing these two parameters, we showed that capsule permeability could be controlled. Promising preliminary data obtained using BPB (Bromophenol Blue) as diffusion marker prompted us to further investigate the antibiotic release of capsules showing the most appropriate release characteristics. PMMA—sorbitol capsules were prepared with wall thickness of 0.5 or 0.6 mm and 60 or 70 w/w% (weight percent) of sorbitol content. In vitro gentamicin, amikacin, tobramycin releases were determined by using a microbiological agar plate diffusion assay. Capsules released 70–100% of their gentamicin load, substantially superior to Septopal, and showed preferable, extended release profiles when compared with the beads. The release kinetics of amikacin and tobramycin closely resembled those of gentamicin. PMMA—sorbitol capsules have been developed and tested, which make them promising devices for local antibiotic delivery.