title: Tuning aerosol particle size distribution of metered dose inhalers using cosolvents and surfactants.
abstract: OBJECTIVE
  The purpose of these studies was to understand the influence of cosolvent and surfactant contributions to particle size distributions emitted from solution metered dose inhalers (pMDIs) based on the propellant HFA 227.
  
  
  METHODS
  Two sets of formulations were prepared: (a) pMDIs-HFA 227 containing cosolvent (5-15% w/w ethanol) with constant surfactant (pluronic) concentration and (b) pMDIs-HFA 227 containing surfactant (0-5.45% w/w pluronic) with constant cosolvent concentration. Particle size distributions emitted from these pMDIs were analyzed using aerodynamic characterization (inertial impaction) and laser diffraction methods.
  
  
  RESULTS
  Both cosolvent and surfactant concentrations were positively correlated with median particle sizes; that is, drug particle size increased with increasing ethanol and pluronic concentrations. However, evaluation of particle size distributions showed that cosolvent caused reduction in the fine particle mode magnitude while the surfactant caused a shift in the mode position. These findings highlight the different mechanisms by which these components influence droplet formation and demonstrate the ability to utilize the different effects in formulations of pMDI-HFA 227 for independently modulating particle sizes in the respirable region.
  
  
  CONCLUSIONS
  Potentially, the formulation design window generated using these excipients in combination could be used to match the particle size output of reformulated products to preexisting pMDI products.
authors.affiliation: School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK. i.saleem@ljmu.ac.uk
authors.forename: Imran Y
authors.initials: IY
authors.lastname: Saleem
authors.forename: Hugh D C
authors.initials: HD
authors.lastname: Smyth
mesh_terms: D000336:Aerosols / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D000431:Ethanol / Q000494:pharmacology; D019793:Fluorescein / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry; D036501:Metered Dose Inhalers; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D012997:Solvents / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*; D005466:Fluorocarbons
chemical_list: D000336:Aerosols; D000431:Ethanol; D019793:Fluorescein; D006845:Hydrocarbons, Fluorinated; D020442:Poloxamer; D012997:Solvents; D013501:Surface-Active Agents; C094049:apaflurane; D005466:Fluorocarbons