title: The mode of drug particle detachment from carrier crystals in an air classifier-based inhaler.
abstract: OBJECTIVE
  To investigate the mode of drug particle detachment from carrier crystals in an air classifier as a function of the carrier size fraction, payload, and the circulation time in the classifier.
  
  
  METHODS
  Laser diffraction analysis of the aerosol cloud from the classifier has been performed at 10, 20, 30, and 60 l/min, using a special adapter, for different adhesive mixture compositions.
  
  
  RESULTS
  A significant part of the drug particles is detached from carrier crystals during inhalation as small agglomerates. Such agglomerates originate from the starting material or are newly formed on the carrier surface during mixing. The degree of agglomeration during mixing depends on the carrier size, payload, and surface rugosity. The size of the agglomerates that are formed during mixing, increases with the size of the carrier particles. Predominantly the largest drug particles and agglomerates are detached within the first 0.5 s of inhalation. After 0.5 s, smaller primary particles are dislodged.
  
  
  CONCLUSIONS
  A high ratio of removal forces to adhesive forces causes a high drug detachment rate from carrier crystals in a classifier within the first 0.5 s of inhalation. The high ratio can be explained by dislodgment of agglomerates and the largest primary particles in the early phases of inhalation. At higher flow rates, detached agglomerates may be further disintegrated into primary particles before they are discharged from the classifier. Agglomeration of drug particles on the carrier surface is the result of the same forces that are responsible for pressing these particles firmly to the carrier crystals during mixing.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, Groningen University Institute for Drug Exploration, 9713 AV Groningen, The Netherlands. A.H.de.Boer@farm.rug.nl
authors.forename: Anne H
authors.initials: AH
authors.lastname: de Boer
authors.forename: Paul
authors.initials: P
authors.lastname: Hagedoorn
authors.forename: Doetie
authors.initials: D
authors.lastname: Gjaltema
authors.forename: Dorette
authors.initials: D
authors.lastname: Lambregts
authors.forename: Meike
authors.initials: M
authors.lastname: Irngartinger
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
mesh_terms: D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics*; D009330:Nebulizers and Vaporizers; D010316:Particle Size
chemical_list: D004337:Drug Carriers