The aim of this work was the investigation of the effects of preparation variables on drug content for the development of capreomycin sulfate (CS) liposomal formulations as potential aerosol antitubercular agents. Dipalmitoylphosphatidylcholine (DPPC), hydrogenated phosphatidylcholine (HPC) and distearoylphosphatidylcholine (DSPC) were used for liposome preparation. A freeze-thawing method was chosen for CS encapsulation. Peptide entrapment, size and morphology were evaluated by UV spectrophotometry, photocorrelation spectroscopy (PCS) and transmission electron microscopy (TEM), respectively. A 2(3) full factorial protocol was designed to evaluate the conditions for CS encapsulation improvement. Peptide content ranged between 1 and 8%. Vesicles showed a narrow size distribution, with average diameters around 1 microm and a good morphology. A mathematical model was generated for each liposomal system and check point analyses revealed good agreement between experimental and predicted values. DPPC liposomes were found to provide the highest CS content. Peptide content was successfully increased by assessing formulation variable effects using a 2(3) factorial design that proved to be a time saving method helpful in developing new CS liposomal formulations for a possible application in aerosol antitubercular therapies.