title: Investigation of the Changes in Aerosolization Behavior Between the Jet-Milled and Spray-Dried Colistin Powders Through Surface Energy Characterization.
abstract: This study aimed to investigate the surface energy factors behind improved aerosolization performance of spray-dried colistin powder formulations compared with those produced by jet milling. Inhalable colistin powder formulations were produced by jet milling or spray drying (with or without l-leucine). Scanning electron micrographs showed the jet-milled particles had irregularly angular shapes, whereas the spray-dried particles were more spherical. Significantly higher fine particle fractions were measured for the spray-dried (43.8%-49.6%) versus the jet-milled formulation (28.4%) from a Rotahaler at 60 L/min; albeit the size distribution of the jet-milled powder was smaller. Surprisingly, addition of l-leucine in the spray drying feed solution gave no significant improvement in fine particle fraction. As measured by inverse gas chromatography, spray-dried formulations had significantly (p < 0.001) lower dispersive, specific, and total surface energy values and more uniform surface energy distributions than the jet-milled powder. Interestingly, no significant difference was measured in the specific and total surface energy values between the spray-dried formulation with or without l-leucine. Based on our previous findings in the self-assembling behavior of colistin in aqueous solution and the surface energy data obtained here, we propose the self-assembly of colistin molecules during spray drying contributed significantly to the reduction of surface free energy and the superior aerosolization performance.
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
authors.forename: Teresa
authors.initials: T
authors.lastname: Jong
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia. Electronic address: david.morton@monash.edu.
authors.forename: David A V
authors.initials: DA
authors.lastname: Morton
authors.affiliation: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907-2091. Electronic address: tonyzhou@purdue.edu.
authors.forename: Qi Tony
authors.initials: QT
authors.lastname: Zhou
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia. Electronic address: ian.larson@monash.edu.
authors.forename: Ian
authors.initials: I
authors.lastname: Larson
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003091:Colistin / Q000737:chemistry*; D058995:Dry Powder Inhalers / Q000379:methods; D007930:Leucine / Q000737:chemistry; D008855:Microscopy, Electron, Scanning / Q000379:methods; D010316:Particle Size; D011208:Powders / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry
chemical_list: D000336:Aerosols; D011208:Powders; D012996:Solutions; D007930:Leucine; D003091:Colistin
keywords: antibiotics; colistin; dry powder inhaler; inverse gas chromatography; jet milling; respiratory infection; self-assembly; spray drying; surface energy