Controlled release antibiotics for dry powder lung delivery.
BACKGROUND
Two controlled release (CR) antibiotics intended for inhalation therapy were evaluated.


METHODS
Ciprofloxacin and doxycycline (both hydrochlorides) were selected as model drugs. Microparticles containing 90:10 ratio of polyvinyl alcohol (PVA) and single antibiotics or combinations were obtained via spray drying. The microparticles were evaluated in terms of particle size, morphology, thermal properties, aerosol performance, and in vitro release.


CONCLUSIONS
Analysis of the microparticle morphology indicated comparable size distributions (2.04 ± 0.06, 2.15 ± 0.01, and 2.21 ± 0.01 μm for ciprofloxacin, doxycycline, and co-spray-dried antibiotic formulations, respectively). Thermal analysis of the microparticles suggested similar responses, which were dominated by the endothermic peaks observed for PVA alone. Analysis of the aerosol performance suggested that the individual antibiotic formulations had different aerosol profiles that were dependent on the antibiotic used. In comparison, the combination CR antibiotics had identical aerosol profiles, suggesting that the microparticles were homogeneous. The release of antibiotics from the CR microparticles showed that ≤ 50% was released over a 6-hour period in comparison to ≥ 90% being released in the first hour for microparticles containing no PVA.


CONCLUSIONS
The potential for antibiotic therapy, and specifically CR antibiotic therapy using dry powder inhalers, provides a promising route for the treatment of pulmonary infection.
Adi
Handoko
H
Advanced Drug Delivery Group, Faculty of Pharmacy-A15, University of Sydney, Sydney, NSW, Australia.
Young
Paul Michael
PM
Chan
Hak-Kim
HK
Salama
Rania
R
Traini
Daniela
D
D000280:Administration, Inhalation; D000336:Aerosols; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations; D004318:Doxycycline / Q000008:administration & dosage* / Q000737:chemistry; D004338:Drug Combinations; D016503:Drug Delivery Systems; D058995:Dry Powder Inhalers; D008168:Lung / Q000378:metabolism; D008863:Microspheres; D010316:Particle Size; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011208:Powders; D013997:Time Factors
D000336:Aerosols; D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D011208:Powders; D002939:Ciprofloxacin; D011142:Polyvinyl Alcohol; D004318:Doxycycline