Epithelial profiling of antibiotic controlled release respiratory formulations

Purpose:Release profiles of two ciprofloxacin hydrochloride formulations for the treatment of respiratory infection were evaluated using different in vitro methodologies and characterised for aerosol performance and toxicity. Methods:Spray-dried ciprofloxacin and ciprofloxacin spraydried with polyvinyl alcohol as a controlled release (CR) agent at a 50:50 w/w ratio were formulated and physico-chemically characterised. Aerosol performances were assessed in vitro using a liquid impinger. Drug release was performed using a modified Franz cell and a validated air interface Calu-3-modified twin stage impinger (TSI). Ciprofloxacin toxicity was also established in vitro. Results: Both formulations had a similar size distribution, while CR ciprofloxacin had superior aerosol performance and stability. The release profiles showed the CR formulation to have a higher transport rate compared to ciprofloxacin alone in the cell model. Contrary results were observed using the diffusion cell. Results: suggest that the air interface cell model provides a more physiologically relevant model than the modified Franz cell. Toxicity analysis showed that the lung epithelial cells could tolerate a wide range of ciprofloxacin concentrations. Conclusions:This study establishes that the in vitro modified TSI air interface Calu-3 model is capable of evaluating the fate of inhaled powder formulations. © Springer Science+Business Media, LLC 2011.