Long-term Storage Stability of Inhalable Phage Powder Formulations: A Four-Year Study

Area of Science:

• Microbiology
• Pharmaceutical Sciences
• Biotechnology

Background:

• Bacteriophage therapy is a promising alternative for multidrug-resistant bacterial pulmonary infections.
• Pulmonary drug delivery requires stable formulations for effective treatment.
• Long-term stability data for spray-dried phage powders is crucial for clinical application.

Purpose of the Study:

• To evaluate the long-term stability of spray-dried bacteriophage (phage) powder formulations for pulmonary delivery.
• To assess the impact of formulation composition (lactose, leucine) on phage bioactivity and physicochemical properties.
• To determine the effects of storage conditions on phage powder stability over four years.

Main Methods:

• Three Pseudomonas aeruginosa phages (PEV1, PEV20, PEV61) were formulated using spray-drying with varying lactose and leucine concentrations.
• Formulations were stored at 4°C/15% RH and 20°C/15% RH for four years.
• Phage viability (titers), particle morphology, and fine particle fraction (FPF) were analyzed over time.

Main Results:

• Phage titers decreased over four years, with reductions ranging from 0.97 to 2.49 log10.
• Formulations containing 70-80% lactose exhibited superior preservation of phage biological activity.
• While particle morphology was largely stable, some elongated features appeared at 20°C/15% RH. Fine particle fraction (FPF) declined significantly from 50-60% to 27-44%.

Conclusions:

• Spray-dried phage powders offer a viable strategy for long-term storage, maintaining bioactivity for potential pulmonary delivery.
• Optimizing lactose concentration is key to enhancing phage stability in dry powder formulations.
• Further research is needed to address the observed decline in aerosol performance (FPF) for effective pulmonary delivery.