Dry powders for the inhalation of ciprofloxacin or levofloxacin combined with a mucolytic agent for cystic fibrosis patients

Objective: This study aimed to design and characterize an inhalable dry powder of ciprofloxacin or levo- floxacin combined with the mucolytics acetylcysteine and dornase alfa for the management of pulmonary infections in patients with cystic fibrosis. Methods: Ball milling, homogenization in isopropyl alcohol and spray drying processes were used to pre- pare dry powders for inhalation. Physico-chemical characteristics of the dry powders were assessed via thermogravimetric analysis, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry and scanning electron microscopy. The particle size distribution, dissolution rate and permeability across Calu-3 cell monolayers were analyzed. The aerodynamic parameters of dry powders were determined using the Andersen cascade impactor (ACI). Results: After the micronization process, the particle sizes of the raw materials significantly decreased. X-ray and DSC results indicated that although ciprofloxacin showed no changes in its crystal structure, the structure of levofloxacin became amorphous after the micronization process. FT-IR spectra exhibited the characteristic peaks for ciprofloxacin and levofloxacin in all formulations. The dissolution rates of micro- homogenized and spray-dried ciprofloxacin were higher than that of untreated ciprofloxacin. ACI results showed that all formulations had a mass median aerodynamic diameter less than 5lm; however, levo- floxacin microparticles showed higher respirability than ciprofloxacin powders did. The permeability of levofloxacin was higher than those of the ciprofloxacin formulations. Conclusion: Together, our study showed that these methods could suitably characterize antibiotic and mucolytic-containing dry powder inhalers.