title: New co-spray-dried tobramycin nanoparticles-clarithromycin inhaled powder systems for lung infection therapy in cystic fibrosis patients.
abstract: The aim of the study was to produce easily dispersible and porous agglomerates of tobramycin nanoparticles surrounded by a matrix composed of amorphous clarithromycin. Nanoparticles of tobramycin with a median particle size of about 400 nm were produced by high-pressure homogenisation. The results from the spray-dried powders showed that the presence of these nanoparticles enhanced powder dispersion during inhalation. Moreover, local drug deposition profiles were similar for the two antibiotics, allowing them to reach the target simultaneously. The dissolution-release profiles showed that tobramycin and clarithromycin might dissolve without any difficulties in the lung. The fine particle fraction increased from 35% and 31% for the physical blend for tobramycin and clarithromycin, respectively, to 63% and 62% for the spray-dried formulation containing nanoparticles. These new formulations, showing high lung deposition properties, even at sub-optimal inspiratory flow rates, represent a great possibility for advancing pulmonary drug administration and local therapy of lung infections.
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Pilcer
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Rémi
authors.initials: R
authors.lastname: Rosière
authors.affiliation: Aptis, Liege, Belgium.
authors.forename: Karl
authors.initials: K
authors.lastname: Traina
authors.affiliation: SMB S.A., Brussels, Belgium.
authors.forename: Thami
authors.initials: T
authors.lastname: Sebti
authors.affiliation: SMB S.A., Brussels, Belgium.
authors.forename: Francis
authors.initials: F
authors.lastname: Vanderbist
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium. Electronic address: kamighi@ulb.ac.be.
authors.forename: Karim
authors.initials: K
authors.lastname: Amighi
mesh_terms: D000280:Administration, Inhalation; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D017291:Clarithromycin / Q000008:administration & dosage* / Q000737:chemistry; D003550:Cystic Fibrosis / Q000150:complications; D003890:Desiccation; D016503:Drug Delivery Systems; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008171:Lung Diseases / Q000150:complications / Q000188:drug therapy*; D053758:Nanoparticles / Q000737:chemistry*; D011208:Powders; D012141:Respiratory Tract Infections / Q000150:complications / Q000188:drug therapy; D012995:Solubility; D014031:Tobramycin / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D011208:Powders; D017291:Clarithromycin; D014031:Tobramycin