title: The rate of drug particle detachment from carrier crystals in an air classifier-based inhaler.
abstract: OBJECTIVE
  To investigate the rate with which drug particles are detached from carrier particles in adhesive mixtures when the action of the separation forces during inhalation is sustained by circulation of the powder dose in an air classifier.
  
  
  METHODS
  Residual drug on retained carrier particles from different adhesive mixture compositions has been analyzed after different circulation times in the classifier (0.5 to 6 s). For calculation of the detachment rate within the first 0.5 s of inhalation, the optical concentration of the aerosol from the classifier has been measured with laser diffraction technique.
  
  
  RESULTS
  Drug detachment from carrier crystals during inhalation increases not only with the flow rate but also with the time during which the action of the separation forces (at a constant flow rate) is sustained. The detachment rate at the same flow rate varies with the carrier size fraction and carrier payload and is clearly highest within the first 0.5 s of inhalation.
  
  
  CONCLUSIONS
  Drug detachment from carrier approaches first-order reaction within the first half-second of inhalation. But at longer circulation times in the classifier, the ratio of removal to adhesive forces decreases dramatically. To increase the detached fraction of drug during inhalation at a constant flow rate, a short residence time for the powder in the de-agglomerator between 0.5 and 2 s is desired.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, Groningen University Institute for Drug Exploration, Ant Deusinglaan 1, 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