Storage stability of inhalable phage powders containing lactose at ambient conditions

Abstract

The aim of this study was to evaluate the storage stability of inhalable phage powders containing lactose and leucine as excipient. As an FDA-approved excipient for inhalation, lactose is preferred over other sugars. PEV phages active against antibiotic-resistant Pseudomonas aeruginosa was spray dried with lactose (55-90%) and leucine (45-10%). Produced powders were heat-sealed in an aluminium pouch at 15% relative humidity (RH) with subsequent storage at 20 °C/60% RH for 12 months. Lactose concentration in the powder positively influenced the phage stability over time. Formulation containing 90% lactose maintained the viability of PEV61 across the study, while ∼1.2 log₁₀ titer reduction was observed in formulations with less lactose. PEV20 was more prone to inactivation (1.7 log₁₀ titer loss at 12-month) when lactose concentration in the particle was below 80%. The fine particle fraction (% wt. particles <5 μm in aerosol) of phage powders was 52-61% and remained the same after 12-month storage. The results demonstrate that spray dried PEV phage powders containing lactose and leucine are biologically and physically stable over long-term storage at ambient temperature. Furthermore, these spray dried phage powders were shown to be non-toxic to lung alveolar macrophage and epithelial cells in vitro.

Keywords: Bacteriophage (Phage); Inhalation aerosol; Lactose; Spray dried powders; Storage stability.