Pulmonary spray dried powders of tobramycin containing sodium stearate to improve aerosolization efficiency.
OBJECTIVE
Tobramycin microparticulate powders containing the hydrophobic adjunct sodium stearate were studied for their use as pulmonary formulations in dry powder inhalers.


METHODS
Spray-dried powders were characterized in terms of particle size distribution, morphology, crystallinity, drug dissolution rate, toxicity on epithelial lung cells and aerosol efficiency.


RESULTS
The presence of the sodium stearate had a direct influence on the aerosol performance of tobramycin spray-dried powders. Powders containing 1% w/w sodium stearate had fine particle fraction FPF of 84.3 +/- 2.0% compared to 27.1 +/- 1.9% for powders containing no adjunct. This was attributed to the accumulation of sodium stearate at the particle surface. Powders with higher sodium stearate concentrations (2% w/w) showed significantly lower FPF (66.4 +/- 0.9%) and less accumulation of sodium stearate at the particle surface. This was attributed to the formation of adjunct micelles, which remained internalised in the particle structure due to their reduced tropism toward the drying drop surface and molecular mobility. Preliminary analysis of the toxicity effect of sodium stearate on A549 cell lines showed that the adjunct, in the concentration used, had no effect on cell viability over a 24-h period compared to particles of pure tobramycin.


CONCLUSIONS
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).
Parlati
Chiara
C
Department of Pharmacy, University of Parma, Parma, Italy.
Colombo
Paolo
P
Buttini
Francesca
F
Young
Paul M
PM
Adi
Handoko
H
Ammit
Alaina J
AJ
Traini
Daniela
D
D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders / Q000737:chemistry / Q000633:toxicity; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects*; D013229:Stearic Acids / Q000737:chemistry* / Q000633:toxicity*; D014031:Tobramycin / Q000008:administration & dosage*; D014961:X-Ray Diffraction
D000336:Aerosols; D000900:Anti-Bacterial Agents; D011208:Powders; D013229:Stearic Acids; C031183:stearic acid; D014031:Tobramycin