Synergistic Combination Dry Powders for Inhaled Antimicrobial Therapy

摘要

Combination products play an important role in medicine as they offer improved clinical effectiveness, enhanced patient adherence, and reduced administrative costs. In combination antimicrobial therapy, the desired outcome is to extend the antimicrobial spectrum and to achieve a possible synergistic effect. However, adverse antagonistic species may sometimes emerge from such combinations, leading to treatment failure. Therefore, it is crucial to screen the drug candidates for compatibility and possible antagonistic interactions. This work aims to develop a novel synergistic dry powder inhaler (DPI) formulation for antimicrobial combination therapy via the pulmonary route. Binary and ternary combinations were prepared via spray drying on a BUCHI? Nano Spray Dryer B-90. All powders were within the respirable size range, and were consisted of spherical particles that were slightly corrugated. The powers yielded fine particle fractions (of the loaded dose) of over 40% when dispersed using an Aerolizer? DPI at 60 L/min. Time-kill studies carried out against common respiratory tract pathogenic bacteria Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia and Acinetobacter baumannii at 1x the minimum inhibitory concentration (MIC) over 24 hours revealed no antagonistic behavior for both combinations. While the interactions were generally found to be indifferent, a favorable synergistic effect was detected in the binary combination when it was tested against Pseudomonas aeruginosa bacteria.