Novel diffusion-dominated mixing for dry powder inhalations development: implementation and mechanistic insights

Area of Science:

• Pharmaceutical Technology
• Biomedical Engineering
• Materials Science

Background:

• Dry powder inhalations (DPIs) require efficient dispersion and adhesion of micronized drug particles.
• Traditional mixing methods can cause shear damage and drug loss.
• Novel shear-free mixing technologies are needed to improve DPI formulation.

Purpose of the Study:

• To investigate the feasibility of Hummer acoustic resonance mixer (HAM) for DPI development.
• To analyze the impact of mixing parameters (time, acceleration) on pulmonary drug delivery efficiency.
• To elucidate the underlying mechanisms of HAM-mediated mixing in DPIs.

Main Methods:

• DPI formulations were prepared using HAM with varying mixing times (5-15 min) and accelerations (30-90 x g).
• Mixing performance was assessed by drug recovery.
• Pulmonary drug delivery efficiency was evaluated macroscopically and microscopically, focusing on particle detachment and deposition.
• Material coverage and adhesive strength were analyzed.

Main Results:

• All HAM formulations showed >95% drug recovery, confirming feasibility.
• Pulmonary drug delivery efficiency decreased with increased acceleration and varied with mixing time.
• Optimal deposition (49.53%) was achieved at 30 x g for 10 min.
• Lower acceleration reduced adhesive strength, facilitating particle detachment in the bronchi.

Conclusions:

• HAM is a feasible and effective technology for DPI development, minimizing drug loss.
• Mixing parameters significantly influence particle detachment and deep lung deposition.
• Weaker adhesive strength, promoted by specific HAM parameters, enhances pulmonary drug delivery.