title: How Much Surface Coating of Hydrophobic Azithromycin Is Sufficient to Prevent Moisture-Induced Decrease in Aerosolisation of Hygroscopic Amorphous Colistin Powder?
abstract: Aerosolisation performance of hygroscopic particles of colistin could be compromised at elevated humidity due to increased capillary forces. Co-spray drying colistin with a hydrophobic drug is known to provide a protective coating on the composite particle surfaces against moisture-induced reduction in aerosolisation performance; however, the effects of component ratio on surface coating quality and powder aerosolisation at elevated relative humidities are unknown. In this study, we have systematically examined the effects of mass ratio of hydrophobic azithromycin on surface coating quality and aerosolisation performance of the co-spray dried composite particles. Four combination formulations with varying drug ratios were prepared by co-spray drying drug solutions. Both of the drugs in each combination formulation had similar in vitro deposition profiles, suggesting that each composite particle comprises two drugs in the designed mass ratio, which is supported by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) data. XPS and ToF-SIMS measurements also revealed that 50% by weight (or 35% by molecular fraction) of azithromycin in the formulation provided a near complete coating of 96.5% (molar fraction) on the composite particle surface, which is sufficient to prevent moisture-induced reduction in fine particle fraction (FPF)recovered and FPFemitted. Higher azithromycin content did not increase coating coverage, while contents of azithromycin lower than 20% w/w did not totally prevent the negative effects of humidity on aerosolisation performance. This study has highlighted that a critical amount of azithromycin is required to sufficiently coat the colistin particles for short-term protection against moisture.
authors.affiliation: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907-2091, USA.|Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Qi Tony
authors.initials: QT
authors.lastname: Zhou
authors.affiliation: Technical Development, Glaxo Wellcome Manufacturing Pte Ltd, 1, Pioneer Sector 1, Jurong, Singapore, 628413, Singapore.
authors.forename: Zhi Hui
authors.initials: ZH
authors.lastname: Loh
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Yu
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Si-Ping
authors.initials: SP
authors.lastname: Sun
authors.affiliation: CSIRO Manufacturing, Bayview Avenue, Clayton, Victoria, 3168, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gengenbach
authors.affiliation: Future Industries Institute, University of South Australia, Mawson Lakes, South Australia, 5095, Australia.
authors.forename: John A
authors.initials: JA
authors.lastname: Denman
authors.affiliation: Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, 19 Innovation Walk, Melbourne, Victoria, 3800, Australia.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia. kim.chan@sydney.edu.au.
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
mesh_terms: D000336:Aerosols; D017963:Azithromycin / Q000032:analysis / Q000737:chemistry*; D003091:Colistin / Q000032:analysis / Q000737:chemistry*; D006813:Humidity / Q000517:prevention & control*; D057927:Hydrophobic and Hydrophilic Interactions; D058427:Hygroscopic Agents / Q000032:analysis / Q000737:chemistry*; D010316:Particle Size; D056951:Photoelectron Spectroscopy; D011208:Powders; D013499:Surface Properties; D014961:X-Ray Diffraction
chemical_list: D000336:Aerosols; D058427:Hygroscopic Agents; D011208:Powders; D017963:Azithromycin; D003091:Colistin
keywords: combination antibiotics; dry powder inhaler; hygroscopic amorphous particle; moisture protection; surface coating