Epithelial Profiling of Antibiotic Controlled Release Respiratory Formulations
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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.
Spray-dried ciprofloxacin and ciprofloxacin spray-dried 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.
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.
This study establishes that the in vitro modified TSI air interface Calu-3 model is capable of evaluating the fate of inhaled powder formulations.
KEY WORDSCalu-3 air interface model ciprofloxacin hydrochloride controlled release dry powder inhaler polyvinyl alcohol
- 4.Salama RO, Traini D, Chan H-K, Young PM. Preparation and characterisation of controlled release co-spray dried drug-polymer microparticles for inhalation 2: evaluation of in vitro release profiling methodologies for controlled release respiratory aerosols. Eur J Pharm Biopharm. 2008;70(1):145–52.PubMedCrossRefGoogle Scholar
- 5.Widdicombe JH. Regulation of the depth and composition of airway surface liquid. J Anat. 2002;201(4):313–8.Google Scholar
- 8.Grainger CI, Greenwell LL, Lockley DJ, Martin GP, Forbes B, Grainger CI, et al. Culture of Calu-3 cells at the air interface provides a representative model of the airway epithelial barrier. Pharm Res. 2006;23(7):1482–90. Comparative Study Research Support, Non-U.S. Gov’t.PubMedCrossRefGoogle Scholar
- 14.Yan Z, Aaron C, Thomas H. Cultured human airway epithelial cells (Calu-3): a model of human respiratory function, structure, and inflammatory responses. Crit Care Res Pract. 2010;2010Google Scholar
- 15.Grainger CI, Greenwell LL, Martin GP, Forbes B. The permeability of large molecular weight solutes following particle delivery to air-interfaced cells that model the respiratory mucosa. Eur J Pharm Sci. 2009;71(2):318–24.Google Scholar
- 17.Adi H, Young PM, Chan H, Stewart P, Agus H, Traini D. Cospray dried antibiotics for dry powder lung delivery. J Pharm Sci. 2007Google Scholar
- 20.Salama R, Hoe S, Chan H-K, Traini D, Young PM. Preparation and characterisation of controlled release co-spray dried drug-polymer microparticles for inhalation 1: influence of polymer concentration on physical and in vitro characteristics. Eur J Pharm Biopharm. 2008;69(2):486–95.PubMedCrossRefGoogle Scholar
- 22.Moore JW, Flanner HH. Mathematical comparison of dissolution profiles. Pharm Technol. 1996;20(6):64–74.Google Scholar
- 27.Administration FaD. Guidance for industry; dissolution testing of immediate release solid oral dosage forms. August 1997Google Scholar