Inhalation of tobramycin in cystic fibrosis. Part 2: optimization of the tobramycin solution for a jet and an ultrasonic nebulizer.
The inhalation of tobramycin is part of current cystic fibrosis (CF) therapy. Local therapy with inhaled antibiotics has demonstrated improvements in pulmonary function. Current inhalation therapy is limited by the available drug formulations in combination with the nebulization time. The aim of this study is to develop a highly concentrated tobramycin solution for inhalation. Several tobramycin solutions, ranging from 5 to 30% (m/v), were compared after aerosolation with a jet and with an ultrasonic nebulizer. Laser diffraction and cascade impactor analysis were used for characterization of the aerosolized solutions. The output rate was determined in volume and mass output per minute. From the output rate measurements, it was concluded that a 20% tobramycin solution is the optimal and maximal concentration to be aerosolized. The jet nebulizer was most suitable. Using the jet nebulizer and the 20% solution, it is possible to administer a dosage of 1000 mg tobramycin by inhalation within 30 min.
Le Brun
P P
PP
Central Hospital Pharmacy The Hague, P.O. Box 43100, 2504 AC, The Hague, The Netherlands.
de Boer
A H
AH
Gjaltema
D
D
Hagedoorn
P
P
Heijerman
H G
HG
Frijlink
H W
HW
D000280:Administration, Inhalation; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation; D003550:Cystic Fibrosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D016231:Fluorescence Polarization Immunoassay; D006801:Humans; D007700:Kinetics; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011312:Pressure; D012996:Solutions; D014031:Tobramycin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D014465:Ultrasonics
D000900:Anti-Bacterial Agents; D012996:Solutions; D014031:Tobramycin