Tuberculosis (TB) is an infectious disease which kills millions of people annually. Two-thirds of TB cases are pulmonary. Current treatment for TB requires high oral and parenteral doses of multiple drugs for 6 to 24 months. Due to toxic side effects, poor adherence to treatment is common and can lead to relapse and the development of drug-resistant strains. We will develop a novel approach to treating TB by evaluating various combinations of four new potent anti-TB drugs formulated in high-dose powders for pulmonary delivery. The formulations will be prepared using a state-of-the-art spray drying technique and the systems will be stabilised. We will evaluate the aerosol performance, dissolution and toxicity of these powders using in vitro techniques and choose the optimum system for evaluation in animal studies and a clinical trial. Direct delivery of these potent anti-TB drugs to the lung will improve efficacy and adherence and reduce systemic toxicity to patients.