title: Co-deposition of a triple therapy drug formulation for the treatment of chronic obstructive pulmonary disease using solution-based pressurised metered dose inhalers.
abstract: OBJECTIVE
  The formulation of multi-drug pressurised metered dose inhalers (pMDIs) opens up exciting therapeutic opportunities for the treatment of asthma and chronic obstructive pulmonary disease (COPD). We have investigated the formulation of a solution-based triple therapy pMDI containing ipratropium, formoterol, budesonide and ethanol as co-solvent.
  
  
  METHODS
  This system was characterised for in-vitro performance and compared with marketed pMDIs (Atrovent and Symbicort).
  
  
  RESULTS
  No significant difference was found in the stage deposition of each drug from the triple therapy formulation, suggesting that the droplets contained a fixed ratio of the three components used. Stage deposition of formoterol and budesonide from the suspension-based marketed Symbicort were significantly different, suggesting that the two drugs were deposited as separate entities. Calculation of the mass median aerodynamic diameter (MMAD) of each formulation suggested Atrovent (ipratropium, MMAD = 0.9 ± 0.0 µm) to have a small particle size, similar to the triple therapy formulation. Atrovent, like the triple therapy formulation was solution based and it contained ethanol as a co-solvent (triple therapy formulation, MMAD = 1.3 ± 0.0 µm).
  
  
  CONCLUSIONS
  This study demonstrated the feasibility of formulating a solution-based pMDI containing a triple therapy with identical deposition pattern for the treatment of several respiratory diseases where multi-drug cell targeting is required.
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Handoko
authors.initials: H
authors.lastname: Adi
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; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry; D019819:Budesonide / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004338:Drug Combinations; D016503:Drug Delivery Systems; D000431:Ethanol / Q000737:chemistry; D004983:Ethanolamines / Q000008:administration & dosage / Q000737:chemistry; D005240:Feasibility Studies; D000068759:Formoterol Fumarate; D006801:Humans; D009241:Ipratropium / Q000008:administration & dosage / Q000737:chemistry; D036501:Metered Dose Inhalers; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012995:Solubility; D012996:Solutions; D012997:Solvents / Q000737:chemistry
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D014677:Pharmaceutical Vehicles; D012996:Solutions; D012997:Solvents; D000431:Ethanol; D019819:Budesonide; D009241:Ipratropium; D000068759:Formoterol Fumarate