Inhaled therapy is potentially more efficient than current oral and parenteral anti-tubercular treatments due to its ability to deliver a higher drug concentration to the lungs. For treating TB, a high dose of the drug (many milligrams) needs to be delivered to the lungs requiring to develop highly aerosolizable powders. This study investigated the influence of lung surfactant, DPPC, on the aerosolization of a first line hydrophilic anti-TB drug, pyrazinamide and a second line relatively hydrophobic drug, moxifloxacin HCl in the presence or absence of L-leucine. Using spray drying, individual powders of supplied pyrazinamide (PSD) and moxifloxacin HCl (MSD) alone and with 10% L-leucine (PL, ML) and 10% DPPC (PLD, MLD) were produced. The powders were characterized for physicochemical properties and aerosolization behaviour. The particle size of all powders except PSD was < 5 μm. The emitted doses of all the spray dried powders were very high (75-89%). The PSD showed poor aerosolization behaviour (FPF of 18.7 ± 3.4%) due to the presence of large (>10 μm) crystalline particles. However, the addition of L-leucine (PL) produced spherical hollow particles and improved aerosolization (FPF 53.0 ± 3.2%). The addition of DPPC and L-leucine to pyrazinamide (PLD) further improved aerosolization (FPF 74.5 ± 5.3%). However, the aerosolization of MSD although increased by the addition of L-leucine (FPF from FPF 55.6 ± 3.3% to 74.1 ± 1.3%), it was not further increased when both DPPC and L-leucine were added. In conclusion, DPPC in the presence of L-leucine significantly increased aerosolization of pyrazinamide, but not of moxifloxacin.