title: Instability of bacteriophages in spray-dried trehalose powders is caused by crystallization of the matrix.
abstract: Spray drying is a valuable technique in pharmaceutical dosage formulation, capable of producing amorphous, spherical powders, suitable for pulmonary deposition and further downstream processing. In this study, we show that spray drying bacteriophages together with trehalose results in an amorphous powder matrix with high glass transition temperature (between 116 and 118°C), typical for amorphous trehalose. These powders are stable at low temperatures (4°C) and relative humidity (0%). However, high humidity causes crystallization of the amorphous matrix, destroying the embedded phages. Furthermore, storage at higher temperature (25°C) causes thermal instability of the embedded phages. The results show that storage conditions are important parameters to take into account in phage therapy development. The resulting particles are hollow spheres, with suitable aerodynamic diameters for deposition into the deep lungs. This opens possibilities to use these phage-containing powder formulations to tackle pulmonary infectious diseases, especially caused by antibiotic resistant pathogens.
authors.affiliation: Laboratory of Gene Technology, Katholieke Universiteit Leuven, Kasteelpark Arenberg 21 - Box 2462, Leuven B-3000, Belgium; Laboratory of Drug Delivery and Disposition, Katholieke Universiteit Leuven, Herestraat 49 - Box 921, Leuven B-3000, Belgium.
authors.forename: Dieter
authors.initials: D
authors.lastname: Vandenheuvel
authors.affiliation: Laboratory of Drug Delivery and Disposition, Katholieke Universiteit Leuven, Herestraat 49 - Box 921, Leuven B-3000, Belgium.
authors.forename: Joke
authors.initials: J
authors.lastname: Meeus
authors.affiliation: Laboratory of Gene Technology, Katholieke Universiteit Leuven, Kasteelpark Arenberg 21 - Box 2462, Leuven B-3000, Belgium.
authors.forename: Rob
authors.initials: R
authors.lastname: Lavigne
authors.affiliation: Laboratory of Drug Delivery and Disposition, Katholieke Universiteit Leuven, Herestraat 49 - Box 921, Leuven B-3000, Belgium. Electronic address: guy.vandenmooter@pharm.kuleuven.be.
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
mesh_terms: D001435:Bacteriophages; D003460:Crystallization; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D006813:Humidity; D011208:Powders / Q000737:chemistry*; D013696:Temperature; D014199:Trehalose / Q000737:chemistry*
chemical_list: D011208:Powders; D014199:Trehalose
keywords: Bacteriophage; Crystallinity; Long-term Storage; Spray drying; Trehalose; Trehalose (PubChem CID: 7427)