Respirable microparticles of aminoglycoside antibiotics for pulmonary administration

In this work aminogycoside antibiotics, with a special focus on tobramycin and amikacin, for DPI products were formulated. In particular, the aim of this study was to investigate the pulmonary administration of aminoglycoside antibiotics as dry powder for the treatment of patients with pulmonary bacterial infection, recurrent or chronic, like bronchiectasis, cystic fibrosis or others. The spray drying process was selected for the production of tobramycin and amikacin micro-particulate powders. Afterwards, the focus of this study was to prepare a series of tobramycin microparticles, with a high aerosolization efficiency and resistance to environmental humidity, using small amounts of lipophilic adjunct such as sodium stearate and a series of fatty acids. These systems were evaluated in terms of particle size distribution by laser diffraction; particle morphology and surface composition by SEM and SEM-EDS, the microparticles were characterised by termogravimetric analysis (TGA), differential scanning calorimetric analysis (DSC) and X-ray analysis. The in vitro aerosol performance was measured by different impactors (TSI, ACI and NGI). The in vitro cell toxicity was evaluated on A549 cell lines. Tobramycin pulmonary powders with low level of sodium stearate, presenting high respiration performances and no overt toxicity on lung cells, could be used to improve therapeutic outcomes of patient with Cystic Fibrosis (CF).