title: Influence of metering chamber volume and water level on the emitted dose of a suspension-based pMDI containing propellant 134a.
abstract: OBJECTIVE
  To determine the influence of metering chamber volume of a valve and water content of an aerosol formulation containing propellant 134a on dose delivery through the valve (DDV) and aerodynamic particle size distribution of the emitted dose.
  
  
  METHODS
  The drug was admixed with ethanol, sonicated, and metered into cans. Valois DF10 RC valves were crimped onto the cans and propellant 134a was gassed through the valve. The DDV was determined using a dosage sampling tube. Aerodynamic particle size distributions were determined by cascade impaction. The water content was determined by Karl Fisher titration.
  
  
  RESULTS
  The DDV increased linearly and the aerodynamic particle size distribution was not influenced as the metering chamber volume of the valve was increased. More drug was emitted from the valve from the initial actuations of the can than from the end. Valves with larger metering chamber volumes demonstrated less variability in DDV than those with smaller metering chamber volumes for the initial actuations. The DDV determined for actuations at the end of the can decreased as water was added extemporaneously. The mass median aerodynamic diameter (MMAD) increased as the water level was increased in the formulation. The geometric standard deviation (GSD) and percent respirable fraction (RF) were not influenced by metering chamber volume or water content.
  
  
  CONCLUSIONS
  The valve chosen for the development of pressurized metered dose inhaler (pMDI) formulations with propellant HFA 134a must be investigated to determine the uniformity of drug delivery. The presence of water influences the characteristics of the emitted dose.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, University of Texas at Austin 78712-1074, USA. WILLIRO@mail.utexas.edu
authors.forename: R O
authors.initials: RO
authors.lastname: Williams
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: J J
authors.initials: JJ
authors.lastname: Koleng
mesh_terms: D000281:Administration, Intranasal; D000335:Aerosol Propellants; D016503:Drug Delivery Systems; D006845:Hydrocarbons, Fluorinated; D010316:Particle Size; D005466:Fluorocarbons
chemical_list: D000335:Aerosol Propellants; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons