Abstract
Inhalation therapy offers several advantages in respiratory disease treatment. Azithromycin is a macrolide antibiotic with poor solubility and bioavailability but with a high potential to be used to fight lung infections. The main objective of this study was to generate a new inhalable dry powder azithromycin formulation. To this end, an electrospray was used, yielding a particle size around 2.5 µm, which is considered suitable to achieve total deposition in the respiratory system. The physicochemical properties and morphology of the obtained microparticles were analysed with a battery of characterization techniques. In vitro deposition assays were evaluated after aerosolization of the powder at constant flow rate (100 L/min) and the consideration of the simulation of two different realistic breathing profiles (healthy and chronic obstructive pulmonary disease (COPD) patients) into a next generation impactor (NGI). The formulation was effective in vitro against two types of bacteria, Staphylococcus aureus and Pseudomonas aeruginosa. Finally, the particles were biocompatible, as evidenced by tests on the alveolar cell line (A549) and bronchial cell line (Calu-3).
Highlights
We aimed to develop an excipient-free dry powder formulation seeking to circumvent the above-mentioned problems of limited antibiotic dose and local conditions generated by the slow solubility of carriers, as well as achieving high bioavailability and reproducibility of the production process
The best conditions were found with chloroform as solvent, since all the azithromycin microparticles (AZT MPs) displayed a round shape and an average size around 2 μm
The antimicrobial activity against S. aureus and P. aeruginosa, two of the main bacteria causing infections in the human respiratory system, was tested and similar minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were found, in comparison to those reported for azithromycin
Summary
The internal lung high surface area (>100 m2 ) allows drugs to be distributed and absorbed efficiently, with high effective drug concentrations reaching the lung This allows for the decrease of the total administered dose, systemic exposure and toxicity, and, as a consequence, the main adverse effects generated by drugs, in particular antibiotics [1,2]. These features are especially interesting in the treatment of pulmonary infections, since local delivery of antibiotics in the lungs could allow for early bacterial eradication and, enable a shorter treatment of minimal systemic exposure. Formulation design, inhalation device and particle size are key issues in determining the aerosol performance of the drug [4]
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