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Author Spotlight: Process Development for the Spray-Drying of Probiotic Bacteria and Evaluation of the Product Quality
Published on: April 7, 2023
Effects of storage conditions on the stability of spray dried, inhalable bacteriophage powders
Sharon S Y Leung1, Thaigarajan Parumasivam1, Fiona G Gao1
1Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.
Abstract:
This study aimed to develop inhalable powders containing phages active against antibiotic-resistant Pseudomonas aeruginosa for pulmonary delivery. A Pseudomonas phage, PEV2, was spray dried into powder matrices comprising of trehalose (0-80%), mannitol (0-80%) and l-leucine (20%). The resulting powders were stored at various relative humidity (RH) conditions (0, 22 and 60% RH) at 4°C. The phage stability and in vitro aerosol performance of the phage powders were examined at the time of production and after 1, 3 and 12 months storage. After spray drying, a total of 1.3 log titer reduction in phage was observed in the formulations containing 40%, 60% and 80% trehalose, whereas 2.4 and 5.1 log reductions were noted in the formulations containing 20% and no trehalose, respectively. No further reduction in titer occurred for powders stored at 0 and 22% RH even after 12 months, except the formulation containing no trehalose. The 60% RH storage condition had a destructive effect such that no viable phages were detected after 3 and 12 months. When aerosolised, the total lung doses for formulations containing 40%, 60% and 80% trehalose were similar (in the order of 105 pfu). The results demonstrated that spray drying is a suitable method to produce stable phage powders for pulmonary delivery. A powder matrix containing ≥40% trehalose provided good phage preservation and aerosol performances after storage at 0 and 22% RH at 4°C for 12 months.
Insights
Stable inhalable phage powders were developed using spray drying for treating antibiotic-resistant Pseudomonas aeruginosa lung infections. Formulations with at least 40% trehalose maintained phage viability and aerosol performance after 12 months of storage.
Area of Science:
- Microbiology
- Pharmaceutical Sciences
- Biotechnology
Background:
- Antibiotic-resistant bacteria, particularly Pseudomonas aeruginosa, pose a significant threat in pulmonary infections.
- Bacteriophages (phages) offer a promising alternative antimicrobial strategy.
- Developing stable phage formulations for effective pulmonary delivery is crucial.
Purpose of the Study:
- To develop inhalable phage powders containing phages active against antibiotic-resistant Pseudomonas aeruginosa for pulmonary delivery.
- To evaluate the stability and aerosol performance of spray-dried phage powders under various storage conditions.
Main Methods:
- Pseudomonas phage PEV2 was spray-dried into powder matrices containing trehalose, mannitol, and l-leucine.
- Powders were stored at 4°C under varying relative humidity (0, 22, and 60% RH).
- Phage stability (titer reduction) and in vitro aerosol performance were assessed over 12 months.
Main Results:
- Spray drying resulted in minimal phage titer reduction (1.3 log) in formulations with ≥40% trehalose.
- Powders stored at 0 and 22% RH showed good phage stability over 12 months, except for formulations without trehalose.
- Storage at 60% RH led to complete loss of viable phages within 3-12 months.
- Formulations with ≥40% trehalose demonstrated comparable aerosol lung doses (approx. 10^5 pfu).
Conclusions:
- Spray drying is a viable method for producing stable phage powders for pulmonary delivery.
- Powder matrices containing ≥40% trehalose ensure good phage preservation and aerosol performance.
- Low relative humidity storage conditions (0-22% RH) at 4°C are optimal for long-term phage powder stability.
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