New inhalation-optimized itraconazole nanoparticle-based dry powders for the treatment of invasive pulmonary aspergillosis

Christophe Duret,1 Nathalie Wauthoz,1 Thami Sebti,2 Francis Vanderbist,2 Karim Amighi11Laboratoire de Pharmacie Gal&eacute;nique et de Biopharmacie, Universit&eacute; Libre de Bruxelles, Brussels, Belgium; 2SMB Laboratoires, Brussels, BelgiumPurpose: Itraconazole (ITZ) dry powders fo...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Duret C, Wauthoz N, Sebti T, Vanderbist F, Amighi K
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a8c277d50ced4dda953e8090747cd924
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a8c277d50ced4dda953e8090747cd924
record_format	dspace
spelling	oai:doaj.org-article:a8c277d50ced4dda953e8090747cd9242021-12-02T01:08:07ZNew inhalation-optimized itraconazole nanoparticle-based dry powders for the treatment of invasive pulmonary aspergillosis1176-91141178-2013https://doaj.org/article/a8c277d50ced4dda953e8090747cd9242012-10-01T00:00:00Zhttp://www.dovepress.com/new-inhalation-optimized-itraconazole-nanoparticle-based-dry-powders-f-a11305https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Christophe Duret,1 Nathalie Wauthoz,1 Thami Sebti,2 Francis Vanderbist,2 Karim Amighi11Laboratoire de Pharmacie Gal&eacute;nique et de Biopharmacie, Universit&eacute; Libre de Bruxelles, Brussels, Belgium; 2SMB Laboratoires, Brussels, BelgiumPurpose: Itraconazole (ITZ) dry powders for inhalation (DPI) composed of nanoparticles (NP) embedded in carrier microparticles were prepared and characterized.Methods: DPIs were initially produced by reducing the ITZ particle size to the nanometer range using high-pressure homogenization with tocopherol polyethylene 1000 succinate (TPGS, 10% w/w ITZ) as a stabilizer. The optimized nanosuspension and the initial microsuspension were then spray-dried with different proportions of or in the absence of mannitol and/or sodium taurocholate. DPI characterization was performed using scanning electron microscopy for morphology, laser diffraction to evaluate the size-reduction process, and the size of the dried NP when reconstituted in aqueous media, impaction studies using a multistage liquid impactor to determine the aerodynamic performance and fine-particle fraction that is theoretically able to reach the lung, and dissolution studies to determine the solubility of ITZ.Results: Scanning electron microscopy micrographs showed that the DPI particles were composed of mannitol microparticles with embedded nano- or micro-ITZ crystals. The formulations prepared from the nanosuspension exhibited good flow properties and better fine-particle fractions, ranging from 46.2% &plusmn; 0.5% to 63.2% &plusmn; 1.7% compared to the 23.1% &plusmn; 0.3% that was observed with the formulation produced from the initial microsuspension. Spray-drying affected the NP size by inducing irreversible aggregation, which was able to be minimized by the addition of mannitol and sodium taurocholate before the drying procedure. The ITZ NP-based DPI considerably increased the ITZ solubility (58 &plusmn; 2 increased to 96 &plusmn; 1 ng/mL) compared with that of raw ITZ or an ITZ microparticle-based DPI (&lt;10 ng/mL).Conclusion: Embedding ITZ NP in inhalable microparticles is a very effective method to produce DPI formulations with optimal aerodynamic properties and enhanced ITZ solubility. These formulations could be applied to other poorly water-soluble drugs and could be a very effective alternative for treating invasive pulmonary aspergillosis.Keywords: aspergillosis, spray-drying, homogenization, inhalation, saturation, solubilityDuret CWauthoz NSebti TVanderbist FAmighi KDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 5475-5489 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Duret C Wauthoz N Sebti T Vanderbist F Amighi K New inhalation-optimized itraconazole nanoparticle-based dry powders for the treatment of invasive pulmonary aspergillosis
description	Christophe Duret,1 Nathalie Wauthoz,1 Thami Sebti,2 Francis Vanderbist,2 Karim Amighi11Laboratoire de Pharmacie Gal&eacute;nique et de Biopharmacie, Universit&eacute; Libre de Bruxelles, Brussels, Belgium; 2SMB Laboratoires, Brussels, BelgiumPurpose: Itraconazole (ITZ) dry powders for inhalation (DPI) composed of nanoparticles (NP) embedded in carrier microparticles were prepared and characterized.Methods: DPIs were initially produced by reducing the ITZ particle size to the nanometer range using high-pressure homogenization with tocopherol polyethylene 1000 succinate (TPGS, 10% w/w ITZ) as a stabilizer. The optimized nanosuspension and the initial microsuspension were then spray-dried with different proportions of or in the absence of mannitol and/or sodium taurocholate. DPI characterization was performed using scanning electron microscopy for morphology, laser diffraction to evaluate the size-reduction process, and the size of the dried NP when reconstituted in aqueous media, impaction studies using a multistage liquid impactor to determine the aerodynamic performance and fine-particle fraction that is theoretically able to reach the lung, and dissolution studies to determine the solubility of ITZ.Results: Scanning electron microscopy micrographs showed that the DPI particles were composed of mannitol microparticles with embedded nano- or micro-ITZ crystals. The formulations prepared from the nanosuspension exhibited good flow properties and better fine-particle fractions, ranging from 46.2% &plusmn; 0.5% to 63.2% &plusmn; 1.7% compared to the 23.1% &plusmn; 0.3% that was observed with the formulation produced from the initial microsuspension. Spray-drying affected the NP size by inducing irreversible aggregation, which was able to be minimized by the addition of mannitol and sodium taurocholate before the drying procedure. The ITZ NP-based DPI considerably increased the ITZ solubility (58 &plusmn; 2 increased to 96 &plusmn; 1 ng/mL) compared with that of raw ITZ or an ITZ microparticle-based DPI (&lt;10 ng/mL).Conclusion: Embedding ITZ NP in inhalable microparticles is a very effective method to produce DPI formulations with optimal aerodynamic properties and enhanced ITZ solubility. These formulations could be applied to other poorly water-soluble drugs and could be a very effective alternative for treating invasive pulmonary aspergillosis.Keywords: aspergillosis, spray-drying, homogenization, inhalation, saturation, solubility
format	article
author	Duret C Wauthoz N Sebti T Vanderbist F Amighi K
author_facet	Duret C Wauthoz N Sebti T Vanderbist F Amighi K
author_sort	Duret C
title	New inhalation-optimized itraconazole nanoparticle-based dry powders for the treatment of invasive pulmonary aspergillosis
title_short	New inhalation-optimized itraconazole nanoparticle-based dry powders for the treatment of invasive pulmonary aspergillosis
title_full	New inhalation-optimized itraconazole nanoparticle-based dry powders for the treatment of invasive pulmonary aspergillosis
title_fullStr	New inhalation-optimized itraconazole nanoparticle-based dry powders for the treatment of invasive pulmonary aspergillosis
title_full_unstemmed	New inhalation-optimized itraconazole nanoparticle-based dry powders for the treatment of invasive pulmonary aspergillosis
title_sort	new inhalation-optimized itraconazole nanoparticle-based dry powders for the treatment of invasive pulmonary aspergillosis
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/a8c277d50ced4dda953e8090747cd924
work_keys_str_mv	AT duretc newinhalationoptimizeditraconazolenanoparticlebaseddrypowdersforthetreatmentofinvasivepulmonaryaspergillosis AT wauthozn newinhalationoptimizeditraconazolenanoparticlebaseddrypowdersforthetreatmentofinvasivepulmonaryaspergillosis AT sebtit newinhalationoptimizeditraconazolenanoparticlebaseddrypowdersforthetreatmentofinvasivepulmonaryaspergillosis AT vanderbistf newinhalationoptimizeditraconazolenanoparticlebaseddrypowdersforthetreatmentofinvasivepulmonaryaspergillosis AT amighik newinhalationoptimizeditraconazolenanoparticlebaseddrypowdersforthetreatmentofinvasivepulmonaryaspergillosis
_version_	1718403276785844224

New inhalation-optimized itraconazole nanoparticle-based dry powders for the treatment of invasive pulmonary aspergillosis

Ejemplares similares