Inhaled mucoactive particles with tailored architecture for enhanced aerodynamicity, stability and efficacy

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Respiratory Medicine

Background:

• Excess mucus production in respiratory diseases like asthma, COPD, chronic bronchitis, and cystic fibrosis (CF) obstructs airways, impairing breathing.
• Mucoactive medications that degrade mucus structure are crucial for managing early symptoms and preventing disease progression.

Purpose of the Study:

• To develop an innovative, multi-benefit inhaled mucoactive dry powder formulation.
• To enhance the aerodynamic properties and efficacy of ambroxol hydrochloride for respiratory conditions.

Main Methods:

• Utilized sodium chloride as an adjuvant to modify the surface architecture of ambroxol hydrochloride particles, creating corrugated, aerodynamically enhanced particles.
• Optimized spray-dried particles for respirable size (d50 of 2.85 ± 0.15 μm).
• Evaluated fine particle fraction (FPF) using an Aerolizer® inhaler and assessed mucolytic potential in artificial sputum medium (ASM).

Main Results:

• Optimized particles exhibited moderate corrugation and respirable size, achieving a ten-fold increase in FPF (~31%) compared to unmodified ambroxol hydrochloride.
• The formulation demonstrated significant potential for mucus liquefaction in ASM.
• The powder formulation showed good flowability and enhanced moisture stability up to ~60% relative humidity (RH).

Conclusions:

• The incorporation of sodium chloride adjuvant significantly improved particle aerodynamicity, flowability, and moisture stability.
• The developed formulation offers synergistic mucolytic properties, indicating its potential as an effective inhaled therapy for mucus-related respiratory disorders.
• This innovative approach provides a multi-faceted benefit for treating conditions characterized by excess mucus production.