Preparation and in vivo evaluation of a dry powder for inhalation of capreomycin.
OBJECTIVE
To develop an aerosol system for efficient local lung delivery of a tuberculostatic drug.


METHODS
The antibiotic, capreomycin sulfate, was spray dried to form a dry powder aerosol. The chemical content and physical properties of resulting particles were assessed under various storage conditions. Plasma concentrations of capreomycin after insufflation into guinea pigs were evaluated at three doses, and compared to IV and IM administration of a capreomycin solution.


RESULTS
Dry powder aerosols containing capreomycin were formulated to enable efficient delivery of large drug masses to the lungs of guinea pigs. Aerosols loaded with 73% CS were shown to possess good aerosolization properties and physical-chemical stability for up to 3 months at room temperature. Upon insufflation into guinea pigs, the amount of CS reaching the bloodstream was significantly lower compared to IV or IM administration, but resulted in a significantly longer drug half-life.


CONCLUSIONS
The results indicate that large doses of capreomycin in dry powder form can be efficiently delivered to the lungs of guinea pigs, which may result in high local drug exposure but significantly reduced systemic exposure as suggested by plasma concentrations in the present studies. These systems have considerable potential to provide more effective therapy for MDR-TB.
School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA. jennifer-fiegel@uiowa.edu
Jennifer
J
Fiegel
Lucila
L
Garcia-Contreras
Matthew
M
Thomas
Jarod
J
VerBerkmoes
Katharina
K
Elbert
Anthony
A
Hickey
David
D
Edwards
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D002207:Capreomycin / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D004355:Drug Stability; D006168:Guinea Pigs; D006207:Half-Life; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods
D000336:Aerosols; D000904:Antibiotics, Antitubercular; D011208:Powders; D002207:Capreomycin