Spray-drying of inhalable, multifunctional formulations for the treatment of biofilms formed in cystic fibrosis.
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Authors
Lababidi, NashrawanOfosu Kissi, Eric
Elgaher, Walid A M
Sigal, Valentin
Haupenthal, Jörg
Schwarz, Bianca C
Hirsch, Anna K H
Rades, Thomas
Schneider, Marc

Issue Date
2019-11-28
Metadata
Show full item recordAbstract
Cystic fibrosis (CF) is a serious lung disease, commonly susceptible to Pseudomonas aeruginosa colonization. The dense mucus together with biofilm formation limit drug permeability and prevent the drug from reaching the site of action, causing treatment failure of the bacterial infection. Besides the use of antibiotics, the mucolytic agent N-acetylcysteine (NAC) is recommended to be co-administered in the treatment of CF. Although several formulations have been developed for inhalation therapy to improve the pulmonary condition in CF patients, there is still no comprehensive study on a combined multifunctional dry powder formulation of antibiotics with NAC. In this work, we developed an innovative multifunctional dry powder inhaler (DPI) formulation based on salt formation between NAC and antibiotics and characterized their solid state properties and physical stability. NAC could be spray dried together with three different antibiotics, azithromycin (Azi), tobramycin (Tobra) and ciprofloxacin (Cipro), without the use of organic solvents to form Azi/NAC, Tobra/NAC and Cipro/NAC DPI formulations. Solid-state characterization of these DPI formulations showed that they were amorphous after spray drying. Azi/NAC and Tobra/NAC form co-amorphous salt systems that were physically stable under storage at stress conditions. For particle characterization, the obtained mass median aerodynamic diameters were in a suitable range for inhalation (< 5.0μm). The multifunctional antibiotic/NAC formulations conserved or improved the antibiotic susceptibility and showed promising results regarding the inhibition of P. aeruginosa PA14 biofilm formation.Citation
Journal of controlled release : official journal of the Controlled Release Society.Affiliation
HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.Publisher
ElsevierJournal
Journal of controlled releasePubMed ID
31654686Type
ArticleLanguage
enISSN
1873-4995ae974a485f413a2113503eed53cd6c53
10.1016/j.jconrel.2019.10.038
Scopus Count
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- Creative Commons
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