Pharmaceutical Research

, Volume 29, Issue 10, pp 2845–2859 | Cite as

New Respirable and Fast Dissolving Itraconazole Dry Powder Composition for the Treatment of Invasive Pulmonary Aspergillosis

  • Christophe DuretEmail author
  • Nathalie Wauthoz
  • Thami Sebti
  • Francis Vanderbist
  • Karim Amighi
Research Paper



Novel itraconazole (ITZ)-based dry powders for inhalation (DPI) were optimized for aerodynamic and dissolution properties and contained excipients that are acceptable for inhalation.


The DPI were produced by spray drying solutions. The drug content, crystallinity state, and morphological evaluation of the dry powders were determined by high performance liquid chromatography, powder X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy, respectively. A particle size analysis was conducted using laser light scattering. The aerodynamic behaviors of the powders were characterized by impaction tests. ITZ dissolution rates were evaluated using a dissolution method adapted to inhaled products.


The DPI presented very high fine particle fractions that ranged from 46.9% to 67.0% of the nominal dose. The formulations showed very fast dissolution rates compared to unformulated crystalline ITZ with the possibility of modulating the dissolution rate by varying the quantity of phospholipids (PL) incorporated. ITZ remained amorphous while the mannitol was crystalline. The α, β and δ-mannitol polymorph ratios varied depending on the formulation compositions.


This formulation strategy could be an attractive alternative for treating invasive pulmonary aspergillosis. The ITZ and PL content are key characteristics because of their influence on the dissolution rate and aerosol performance.


dry powder for inhalation (DPI) invasive aspergillosis itraconazole mannitol polymorphism 



active pharmaceutical ingredient


Carr’s index


aerodynamic diameter


dry powder(s) for inhalation


emitted dose


Food and Drug Administration


fine particle dose


fine particle fraction


invasive aspergillosis




International Center for Diffraction Data






minimal inhibitory concentration


multi-stage liquid impactor


modulated temperature differential scanning calorimetry


next generation impactor




particle size distribution


powder X-ray diffraction


reference intensity ratio


round per minute


spray dried


scanning electron microscopy


thermogravimetric analysis


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Christophe Duret
    • 1
    Email author
  • Nathalie Wauthoz
    • 1
  • Thami Sebti
    • 2
  • Francis Vanderbist
    • 2
  • Karim Amighi
    • 1
  1. 1.Laboratoire de Pharmacie Galénique et de BiopharmacieUniversité Libre de BruxellesBrusselsBelgium
  2. 2.Laboratoires SMB S.A.BrusselsBelgium

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