title: CLSM as quantitative method to determine the size of drug crystals in a solid dispersion.
abstract: OBJECTIVE
  To test whether confocal laser scanning microscopy (CLSM) can be used as an analytical tool to determine the drug crystal size in a powder mixture or a crystalline solid dispersion.
  
  
  METHODS
  Crystals of the autofluorescent drug dipyridamole were incorporated in a matrix of crystalline mannitol by physical mixing or freeze-drying. Laser diffraction analysis and dissolution testing were used to validate the particle size that was found by CLSM.
  
  
  RESULTS
  The particle size of the pure drug as determined by laser diffraction and CLSM were similar (D(50) of approximately 22 μm). CLSM showed that the dipyridamole crystals in the crystalline dispersion obtained by freeze-drying of less concentrated solutions were of sub-micron size (0.7 μm), whereas the crystals obtained by freeze-drying of more concentrated solutions were larger (1.3 μm). This trend in drug crystal size was in agreement with the dissolution behavior of the tablets prepared from these products.
  
  
  CONCLUSIONS
  CLSM is a useful technique to determine the particle size in a powder mixture. Furthermore, CLSM can be used to determine the drug crystal size over a broad size distribution. A limitation of the method is that the drug should be autofluorescent.
authors: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713, AV, Groningen, The Netherlands. h.de.waard@rug.nl
authors: Hans
authors: H
authors: de Waard
authors: Martin J T
authors: MJ
authors: Hessels
authors: Maarten
authors: M
authors: Boon
authors: Klaas A
authors: KA
authors: Sjollema
authors: Wouter L J
authors: WL
authors: Hinrichs
authors: Anko C
authors: AC
authors: Eissens
authors: Henderik W
authors: HW
authors: Frijlink
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