Storage stability of phage-ciprofloxacin combination powders against Pseudomonas aeruginosa respiratory infections

Storage stability of phage-ciprofloxacin combination powders against Pseudomonas aeruginosa respiratory infections.

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Item Type: Article
Status: Published
Official URL:
Journal or Publication Title: International Journal of Pharmaceutics
Volume: 591
Page Range: p. 119952
Date: 2020
Divisions: Tuberculosis
Depositing User: General Admin
Identification Number: 10.1016/j.ijpharm.2020.119952
ISSN: 03785173
Date Deposited: 29 Mar 2021 05:55

Novel inhalable and synergistic combination powder formulations of phage PEV20 and ciprofloxacin were recently developed to treat Pseudomonas aeruginosa respiratory infections. In the present study, we investigated the storage stability of these powders which comprised ciprofloxacin, lactose and L-leucine in mass ratios of 1:1:1 (Formulation A) or ciprofloxacin and L-leucine in 2:1 without lactose (Formulation B). These powders were produced by spray drying, collected in polypropylene tubes and packed inside aluminium pouches which were heat-sealed at < 20% relative humidity (RH), then stored at 4 °C or 25 °C. The phage viability, aerosol performance and solid-state properties of the powders were examined over 12 months. The biological activity and aerosol performance of both formulations showed no significant change over 12 months of storage at 4 °C. However, after four months of storage at 25 °C, a significant titer loss of 2.2 log10 (p < 0.01) was observed in Formulation B, but the loss in Formulation A was much less (0.5 log10 (p < 0.05)). In contrast, the fine particle fraction (FPF, wt. % particles ≤ 5 µm) of Formulation A was significantly reduced by 11% (p < 0.05) after four months of storage at 25 °C, whereas the aerosol performance of Formulation B remained stable over 12 months. The results showed that ciprofloxacin can sufficiently stabilize phage through vitrification and/or hydrogen bonding at 4 °C. The presence of lactose was beneficial to preserve the phage at 25 °C. In conclusion, spray dried PEV20-ciprofloxacin combination powders were biologically and physico-chemically stable even without lactose as a stabilising excipient, when stored below 20% RH at 4 °C for 12 months.

Keywords: Bacteriophage (phage); Ciprofloxacin; Dry powder inhalation; Inhalation aerosol formulation; Pseudomonas aeruginosa; Respiratory infection.

Copyright © 2020 Elsevier B.V. All rights reserved.

Lin, Yu
Yoon Kyung Chang, Rachel
Britton, Warwick J
Morales, Sandra
Kutter, Elizabeth
Li, Jian
Chan, Hak-Kim
Last Modified: 29 Mar 2021 05:55

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