title: Micronized drug powders in binary mixtures and the effect of physical properties on aerosolization from combination drug dry powder inhalers.
abstract: OBJECTIVE
  To evaluate physicochemical properties of two micronized drugs, salbutamol sulfate (SS) and beclomethasone dipropionate (BDP) prepared as dry powder inhalation physical blends.
  
  
  METHODS
  Five different blends of SS:BDP ratios of 0:100, 25:75, 50:50, 75:25, and 100:0 (w/w) were prepared. Aerosolization performance was evaluated using a multistage impinger and a Rotahaler® device.
  
  
  RESULTS
  The median SS particle diameter was larger than BDP (4.33 ± 0.37 µm compared to 2.99 ± 0.15 µm, respectively). The SS appeared to have a ribbon-like morphology, while BDP particles had plate-like shape with higher cohesion than SS. This was reflected in the aerosolization performance of the two drugs alone, where SS had a significantly higher fine particle fraction (FPF) than BDP (12.3%, 3.1% and 2.9%, 0.2%, respectively). The study of cohesion versus adhesion for a series of SS and BDP probes on SS and BDP substrates suggested both to be moderately adhesive, verified using scanning Raman microscopy, where a physical association between the two was observed. A plot of loaded versus emitted dose indicated that powder bed fluidization was significantly different when the drugs were tested individually. Furthermore, the FPF of the two drugs from the binary blends, at all three ratios, were similar.
  
  
  CONCLUSIONS
  Such observations indicate that when these two drugs are formulated as a binary system, the resulting powder structure is altered and the aerosolization performance of each drug is not reflective of the individual drug performance. Such factors could have important implications and should be considered when developing combination dry powder inhalation systems.
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Jetmalani
authors.forename: P M
authors.initials: PM
authors.lastname: Young
authors.forename: T
authors.initials: T
authors.lastname: Smith
authors.forename: P
authors.initials: P
authors.lastname: Stewart
authors.forename: D
authors.initials: D
authors.lastname: Traini
mesh_terms: D000280:Administration, Inhalation; D000420:Albuterol / Q000008:administration & dosage* / Q000737:chemistry; D000704:Analysis of Variance; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000737:chemistry; D001507:Beclomethasone / Q000008:administration & dosage* / Q000737:chemistry; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry; D055598:Chemical Phenomena; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D058995:Dry Powder Inhalers; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D011208:Powders; D001507:Beclomethasone; D000420:Albuterol