Formulation and characterization of lipid-coated tobramycin particles for dry powder inhalation.
OBJECTIVE
This study was conducted to develop and evaluate the physicochemical and aerodynamic characteristics of lipid-coated dry powder formulations presenting particularly high lung deposition.


METHODS
Lipid-coated particles were prepared by spray-drying suspensions with different concentrations of tobramycin and lipids. The solid-state properties of the formulations, including particle size and morphology, were assessed by scanning electron microscopy and laser diffraction. Aerosol performance was studied by dispersing the powders into a Multistage Liquid Impinger and determining drug deposition by high-performance liquid chromatography.


RESULTS
Particle size distributions of the formulations were unimodal, narrow with more than 90% of the particles having a diameter of less than 2.8 microm. All powder formulations exhibited mass median diameters of less than 1.3 and 3.2 microm, as determined by two different laser diffraction methods, the Malvern's Mastersizer and Spraytec, respectively. The fine particle fraction varied within a range of 50.5 and 68.3%.


CONCLUSIONS
Lipid coating of tobramycin formulations resulted in a reduced agglomeration tendency and in high fine particle fraction values, thus improving drug deposition. The very low excipients content (about 5% m/m) of these formulations offers the benefit of delivering particularly huge concentrations of antibiotic directly to the site of infection, while minimizing systemic exposure, and may provide a valuable alternative treatment of cystic fibrosis.
Pilcer
Gabrielle
G
Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles, Belgium.
Sebti
Thami
T
Amighi
Karim
K
D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D005612:Freeze Drying; D008055:Lipids / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D033362:Powder Diffraction; D011208:Powders; D012137:Respiratory System; D013499:Surface Properties; D013678:Technology, Pharmaceutical; D014031:Tobramycin / Q000008:administration & dosage / Q000737:chemistry*
D000336:Aerosols; D000900:Anti-Bacterial Agents; D008055:Lipids; D011208:Powders; D014031:Tobramycin