title: Agglomerate properties and dispersibility changes of salmeterol xinafoate from powders for inhalation after storage at high relative humidity.
abstract: OBJECTIVE
  This study investigated changes in agglomeration and the mechanism of dispersibility decrease of salmeterol xinafoate (SX) from SX-lactose mixtures for inhalation after storage at 75% RH for 3 months.
  
  
  METHODS
  The dispersibility, PSD and in situ PSD of aerosol plumes of SX alone and SX-coarse lactose (CL) mixtures containing 0, 5, 10 and 20% micronized lactose (ML) before and after storage were determined by a Next Generation Impactor (NGI), a Mastersizer 2000 and a Spraytec, respectively.
  
  
  RESULTS
  The PSD of ML increased after storage at 75% RH, but dispersibility of SX using the stored ML increased. After storage, the %SX of the mixture containing 20% ML (M20F) significantly increased (P<0.05) in the throat and mouthpiece, preseparator and stage 1 of NGI, while it significantly decreased in the remaining stages (P<0.05). In situ analysis of aerosol plumes of M20F supported this result with an increased presence of particles of 4-25microm and a decreased respirable particle distribution of <4microm after storage.
  
  
  CONCLUSIONS
  The decreased dispersibility of M20F after storage was due to the formation of less dispersible agglomerates, probably occurring through enhanced capillary interaction and/or solid bridging of ML, entrapping and preventing the release of SX particles.
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Victoria 3052, Australia.
authors.forename: Shyamal
authors.initials: S
authors.lastname: Das
authors.forename: Ian
authors.initials: I
authors.lastname: Larson
authors.forename: Paul
authors.initials: P
authors.lastname: Young
authors.forename: Peter
authors.initials: P
authors.lastname: Stewart
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients; D006813:Humidity; D007785:Lactose; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders; D011312:Pressure; D000068299:Salmeterol Xinafoate
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D005079:Excipients; D011208:Powders; D000068299:Salmeterol Xinafoate; D007785:Lactose; D000420:Albuterol