title: Particle synergy and aerosol performance in non-aqueous liquid of two combinations metered dose inhalation formulations: an AFM and Raman investigation.
abstract: The drug-drug interaction of two pMDI (pressure metered dose inhaler) combination products budesonide-formoterol fumarate dihydrate and salmeterol xinafoate-fluticasone propionate were investigated using in situ atomic force microscopy (AFM), equipped with a liquid cell filled with model a propellant, and Raman spectroscopy. Electron microscopy images of the budesonide-formoterol formulation suggested discrete particulates while the salmeterol-fluticasone formulation appeared agglomerated. Based on the analysis of the AFM curves, it is proposed that interactions in the budesonide-formoterol system (cohesion and adhesion) are dominated by van der Waals forces while interactions between salmeterol and fluticasone are of a chemical nature. Such observations are further substantiated by analysis of the Raman maps produced from pMDI actuations deposited on Andersen cascade impactor plates. The relevance of such synergy between particulates of different chemical nature is discussed. In particular, it is anticipated that strong interactions between particles could lead to heteroflocculation, increase aerosol particle size and consequently reduction of the respirable fine particle fraction.
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia. philippe.rogueda@monash.edu
authors.forename: Philippe G A
authors.initials: PG
authors.lastname: Rogueda
authors.forename: Robert
authors.initials: R
authors.lastname: Price
authors.forename: Tim
authors.initials: T
authors.lastname: Smith
authors.forename: Paul M
authors.initials: PM
authors.lastname: Young
authors.forename: Daniela
authors.initials: D
authors.lastname: Traini
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage / Q000627:therapeutic use; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use; D001982:Bronchial Diseases / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D019819:Budesonide / Q000008:administration & dosage / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage / Q000627:therapeutic use; D000068298:Fluticasone; D000068759:Formoterol Fumarate; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage / Q000737:chemistry*; D036501:Metered Dose Inhalers; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D000068299:Salmeterol Xinafoate; D013059:Spectrum Analysis, Raman
chemical_list: D000336:Aerosols; D000730:Androstadienes; D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D006845:Hydrocarbons, Fluorinated; D019819:Budesonide; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol; D000068759:Formoterol Fumarate