title: Hollow porous particles in metered dose inhalers.
abstract: OBJECTIVE
  To assess the physical stability and aerosol characteristics of suspensions of hollow porous microspheres (PulmoSpheres) in HFA-134a.
  
  
  METHODS
  Cromolyn sodium, albuterol sulfate, and formoterol fumarate microspheres were prepared by a spray-drying method. Particle size and morphology were determined via electron microscopy. Particle aggregation and suspension creaming times were assessed visually, and aerosol performance was determined via Andersen cascade impaction and dose uniformity studies.
  
  
  RESULTS
  The hollow porous particle morphology allows the propellant to permeate freely within the particles creating a novel form of suspension termed a homodispersion, wherein the dispersed and continuous phases are identical, separated by an insoluble interfacial layer of drug and excipient. Homodispersion formation improves suspension stability by minimizing the difference in density between the particles and the medium, and by reducing attractive forces between particles. The improved physical stability leads to excellent dose uniformity. Excellent aerosolization efficiencies are also observed with PulmoSpheres formulations, with fine particle fractions of about 70%.
  
  
  CONCLUSIONS
  The formation of hollow porous particles provides a new formulation technology for stabilizing suspensions of drugs in hydrofluoroalkane propellants with improved physical stability, content uniformity, and aerosolization efficiency.
authors.affiliation: Alliance Pharmaceutical Corp., San Diego, California 92121, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Dellamary
authors.forename: T E
authors.initials: TE
authors.lastname: Tarara
authors.forename: D J
authors.initials: DJ
authors.lastname: Smith
authors.forename: C H
authors.initials: CH
authors.lastname: Woelk
authors.forename: A
authors.initials: A
authors.lastname: Adractas
authors.forename: M L
authors.initials: ML
authors.lastname: Costello
authors.forename: H
authors.initials: H
authors.lastname: Gill
authors.forename: J G
authors.initials: JG
authors.lastname: Weers
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000493:pharmacokinetics; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D004205:Cromolyn Sodium / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004983:Ethanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics; D000068759:Formoterol Fumarate; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung; D008854:Microscopy, Electron; D008863:Microspheres; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders
chemical_list: D000336:Aerosols; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D004983:Ethanolamines; D011208:Powders; D004205:Cromolyn Sodium; D000420:Albuterol; D000068759:Formoterol Fumarate