Current Fungal Infection Reports

, Volume 8, Issue 4, pp 331–342 | Cite as

Recent Developments in Inhaled Triazoles Against Invasive Pulmonary Aspergillosis

  • Romain Merlos
  • Karim Amighi
  • Nathalie WauthozEmail author
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Invasive pulmonary aspergillosis (IPA) is a fungal infection that is seen with particular frequency in immunocompromised patients, and associated with high rates of mortality. To combat or prevent IPA, triazoles such as voriconazole or itraconazole and posaconazole have become accepted as first- and second-line therapy, respectively. However, triazoles are associated with issues of oral bioavailability, high liver metabolism, and/or drug–drug interactions, increasing the variability of systemic concentrations. As a way to overcome these issues, inhalation appears to be a promising route for delivery of triazoles for prophylactic or curative therapy in IPA. Indeed, pulmonary drug delivery drastically increases the drug in situ while decreasing the systemic exposure, thereby limiting drug metabolization, side effects, and drug–drug interactions. The development of triazoles for inhalation has focused on voriconazole and itraconazole, drugs which are both highly permeable but with significant different solubility. In this review, we describe the most advanced and promising pharmaceutical developments for voriconazole and itraconazole.


Aerosol Antifungal Aspergillosis Fungal infection Pulmonary delivery Dry powder inhaler Dry powder for inhalation Nebulizer Nebulization Cyclodextrin Nanoparticle Solid dispersion Controlled-release drug delivery 



amorphous itraconazole with Phospholipon® 90H


amorphous itraconazole


amorphous itraconazole nanoparticle-based aggregates


itraconazole nanoparticle-based aggregates with polysorbate 20


itraconazole nanoparticle-based aggregates with polysorbate 80 and Poloxamer 407


amphotericin B deoxycholate


area under the curve


maximum peak concentration


crystalline itraconazole


crystalline itraconazole nanoparticles


crystalline itraconazole nanoparticle-based aggregates


aerodynamic diameter


dry powder inhaler


fine particle fraction


hydroxypropyl -β-cyclodextrin


amorphous itraconazole-based inclusion complex with HPβCD


invasive pulmonary aspergillosis


International Pharmaceutical Excipients Council




minimum inhibitory concentration


median mass aerodynamic diameter


polyethylene glycol




saturation solubility equilibrium


sulfobutyl ether-β-cyclodextrin


terminal half-life





The authors would like to thank Dr. PO Gubbins of the University of Missouri–Kansas City for his review of the manuscript.

Compliance with Ethics Guidelines

Conflict of Interest

R. Merlos received a PhD grant from "Région Wallonne" for a subcontracting project with Galephar Pharmaceutical and Université Libre de Bruxelles.

K. Amighi and N. Wauthoz both declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


The findings and conclusions in this report are those of the author(s).


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Laboratory of Pharmaceutics and Biopharmaceutics, Faculty of PharmacyUniversité Libre de BruxellesBrusselsBelgium

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