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Sterilization of necrotic granulomas containing Mycobacterium tuberculosis is difficult by oral and parenteral drug delivery of antitubercular drugs. Pulmonary delivery of these drugs should increase the concentration of drug in the granulomas and, thereby, improve the sterilization. The current study aimed to develop spray-dried (SD) powders composed of pyrazinamide, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine N-(carbonyl-methoxy polyethylene glycol-2000) (DSPE-PEG2k) and l-leucine to improve drug delivery to the deeper lung. Pyrazinamide SD powders with varying amounts of DPPC (5, 15 and 25% w/w) were produced using a BUCHI B-290 Mini Spray-Dryer. The powders were characterized physicochemically and for their aerosol dispersion performance using a Next Generation Impactor (NGI). All the SD powders had a narrow particle size distribution (1.29–4.26 μm) with low residual moisture (<2%). Solid state characterization confirmed that the α-polymorphic crystalline pyrazinamide transformed into the γ-polymorphic form during spray-drying. SD pyrazinamide (PDDL0) without excipients showed very poor aerosolization with a fine particle fraction (FPF%) of 8.5 ± 1.0%. However, the SD powder with 25% w/w DPPC (PDDL3) exhibited the best aerosolization with a FPF of 73.2 ± 4.0%. Incorporating high amounts of DPPC improved aerosolization of SD powders; however further evaluation of the developed inhalation powders is necessary to determine their therapeutic potential for treating pulmonary tuberculosis.