caa a22 4500 44531317X CHVBK 20180317142637.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s11095-011-0484-8 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0484-8 CLSM as Quantitative Method to Determine the Size of Drug Crystals in a Solid Dispersion [Elektronische Daten] [Hans de Waard, Martin Hessels, Maarten Boon, Klaas Sjollema, Wouter Hinrichs, Anko Eissens, Henderik Frijlink] ABSTRACT: Purpose: 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 (D50 of approximately 22μm). CLSM showed that the dipyridamole crystals in the crystalline dispersion obtained by freeze-drying of less concentrated solutions were of sub-micron size (0.7μm), whereas the crystals obtained by freeze-drying of more concentrated solutions were larger (1.3μm). This trend in drug crystal size was in agreement with the dissolution behavior of the tablets prepared from these products. Conclusion: 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. The Author(s), 2011 confocal laser scanning miscroscopy nationallicence controlled crystallization during freeze-drying nationallicence dipyridamole nationallicence dissolution nationallicence freeze-drying nationallicence de Waard Hans Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713, Groningen, AV, The Netherlands aut Hessels Martin Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713, Groningen, AV, The Netherlands aut Boon Maarten Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713, Groningen, AV, The Netherlands aut Sjollema Klaas Microscopy and Imaging Center, University Medical Center Groningen, Antonius Deusinglaan 1, 9713, Groningen, AV, The Netherlands aut Hinrichs Wouter Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713, Groningen, AV, The Netherlands aut Eissens Anko Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713, Groningen, AV, The Netherlands aut Frijlink Henderik Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713, Groningen, AV, The Netherlands aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/10(2011-10-01), 2567-2574 0724-8741 28:10<2567 2011 28 11095 https://doi.org/10.1007/s11095-011-0484-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0484-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- de Waard Hans Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713, Groningen, AV, The Netherlands aut NATIONALLICENCE 700 1- Hessels Martin Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713, Groningen, AV, The Netherlands aut NATIONALLICENCE 700 1- Boon Maarten Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713, Groningen, AV, The Netherlands aut NATIONALLICENCE 700 1- Sjollema Klaas Microscopy and Imaging Center, University Medical Center Groningen, Antonius Deusinglaan 1, 9713, Groningen, AV, The Netherlands aut NATIONALLICENCE 700 1- Hinrichs Wouter Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713, Groningen, AV, The Netherlands aut NATIONALLICENCE 700 1- Eissens Anko Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713, Groningen, AV, The Netherlands aut NATIONALLICENCE 700 1- Frijlink Henderik Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713, Groningen, AV, The Netherlands aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/10(2011-10-01), 2567-2574 0724-8741 28:10<2567 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer