Purpose: The potential for rifapentine-containing oral therapeutic regimens to significantly shorten the current six-month anti-tubercular treatment regimen is confounded by high plasma protein binding of rifapentine. Inhaled aerosol delivery of rifapentine, a more potent anti-tubercular antibiotic drug, in combination with other first- line antibiotics may overcome this limitation to deliver a high drug dose at the pulmonary site of infection. Method: A formulation consisting of rifapentine, moxifloxican and pyrazinamide with and without leucine was prepared by spray-drying. This formulation was assessed for its physico-chemical properties, and in vitro aerosol performance and antimicrobial activity. Results: The antibiotic powders, with and without leucine, had similar median aerodynamic diameters of 2.58 ± 0.08 μm and 2.51 ± 0.06 μm, with a relatively high fine particle fraction of 55.5 ± 1.9% and 63.6 ± 2.0%, respectively. Although the powders were mostly amorphous, some crystalline peaks associated with the δ polymorph for the spray-dried crystalline pyrazinamide were identified. Conclusions: Stabilisation of the powder with 10% w/w leucine and protection from moisture ingress was found to be necessary to prevent the crystallisation of pyrazinamide after long-term storage. In vitro biological assays indicated antimicrobial activity was retained after spray-drying. Murine pharmacokinetic studies are currently underway.