Development and Characterization of Spray-Dried Combined Levofloxacin-Ambroxol Dry Powder Inhaler Formulation

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Respiratory Medicine

Background:

• Development of novel drug delivery systems for lower respiratory tract infections (LRTIs).
• Exploration of composite microparticles combining levofloxacin (antibiotic) and ambroxol (mucolytic with antibacterial properties).

Purpose of the Study:

• To develop and characterize spray-dried composite microparticles of levofloxacin and ambroxol for LRTIs.
• To optimize the drug ratio and evaluate the effect of leucine as a dispersibility enhancer.

Main Methods:

• Spray-drying of levofloxacin-ambroxol composite microparticles at various mass ratios (1:1, 1:0.5, 1:0.25), with and without leucine.
• Characterization using ATR-FTIR, SEM, PXRD, and TGA.
• In vitro aerosolization performance assessment using a twin-stage impinger and RP-HPLC for drug quantification.

Main Results:

• Spherical microparticles (1.9-2.9 µm) achieved, suitable for deep lung deposition.
• Leucine significantly improved yield, flow properties, and aerosolization.
• The 1:1 levofloxacin to ambroxol ratio demonstrated optimal flow and fine particle fractions (FPFs).
• Addition of 5% leucine significantly enhanced FPFs, likely via increased surface hydrophobicity.

Conclusions:

• Spray-dried composite microparticles of levofloxacin and ambroxol show significant potential for efficient lung delivery.
• Optimized formulation with leucine is promising for managing LRTIs.
• Balanced drug ratios are crucial for achieving desired particle characteristics and aerosolization performance.