The aim of the work was to produce inhalable capreomycin powders using a novel spray-drying technology. A 23 factorial design was used to individuate the best working conditions. The maximum desirability was identified at the smallest mean volume diameter (dv) and span, and the highest yield. Powders were characterized for size, morphology, flowability and aerodynamic properties. Mathematical models showed a good predictivity with biases lower than 20%. The maximum conformity with desirability criteria was obtained spraying a 10 mg/mL bacitracin solution at 111 °C with the 4 μm pore size membrane. By processing capreomycin sulfate with the parameters optimized for bacitracin, an inhalable powder was obtained (i.e., yield of 82%, dv of 3.83 μm, and span of 1.04). By further optimization, capreomycin sulfate powder characteristics were improved (i.e., yield, ˜71%; dv, 3.25 μm; span, 0.95). After formulation with lactose, emitted dose and respirable fraction of 87% and ˜27% were obtained, respectively. Two capreomycin sulfate powders with suitable properties for inhalation were produced using the nano spray-dryer B-90.