title: Carrier-free combination for dry powder inhalation of antibiotics in the treatment of lung infections in cystic fibrosis.
abstract: The aim of the study was to develop an efficient combination antibiotic formulation containing tobramycin and clarithromycin as a dry powder for inhalation. A carrier-free formulation of the two drugs was produced by spray-drying and characterised for its aerodynamic behaviour by impaction tests with an NGI and release profiles. The particle size distribution, morphological evaluation and crystallinity state were determined by laser diffraction, scanning electron microscopy and powder X-ray diffraction, respectively. Drug deposition profiles were similar for the two antibiotics, which has a synergistic effect, allowing them to reach the target simultaneously at the expected dose. The release profiles show that tobramycin and clarithromycin should probably dissolve without any difficulties in vivo in the lung as 95% of tobramycin and 57% of clarithromycin mass dissolved in 10min for the spray-dried formulation. The FPF increased from 35% and 31% for the physical blend for tobramycin and clarithromycin, respectively, to 65% and 63% for the spray-dried formulation. The spray-dried formulation shows particularly high deposition results, even at sub-optimal inspiratory flow rates, and therefore, represents an attractive alternative in the local treatment of lung infection such as in cystic fibrosis.
authors: Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles-ULB, Brussels, Belgium. gpilcer@ulb.ac.be
authors: Gabrielle
authors: G
authors: Pilcer
authors: Véronique
authors: V
authors: De Bueger
authors: Karl
authors: K
authors: Traina
authors: Hamidou
authors: H
authors: Traore
authors: Thami
authors: T
authors: Sebti
authors: Francis
authors: F
authors: Vanderbist
authors: Karim
authors: K
authors: Amighi
mesh_terms: D000280:Administration, Inhalation; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001424:Bacterial Infections / Q000188:drug therapy / Q000209:etiology; D017291:Clarithromycin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003460:Crystallization; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy; D004338:Drug Combinations; D004339:Drug Compounding; D004357:Drug Synergism; D058995:Dry Powder Inhalers; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000188:drug therapy / Q000382:microbiology; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders; D014018:Tissue Distribution; D014031:Tobramycin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D011208:Powders; D017291:Clarithromycin; D014031:Tobramycin