Please use this identifier to cite or link to this item: doi:10.22028/D291-29605
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Title: The influence of mannitol on morphology and disintegration of spray-dried nano-embedded microparticles
Author(s): Torge, Afra
Grützmacher, Philipp
Mücklich, Frank
Schneider, Marc
Language: English
Title: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Volume: 104
Startpage: 171
Endpage: 179
Publisher/Platform: Elsevier
Year of Publication: 2017
Publikation type: Journal Article
Abstract: Nano-embedded microparticles represent a promising approach to deliver nanoparticles to the lungs. Microparticles with an appropriate aerodynamic diameter enable an application by dry powder inhaler and the transport of nanoparticles into the airways. By disintegration after deposition, nanoparticles can be released to exhibit their advantages such as a sustained drug release and delivery of the drug across the mucus barrier. The use of an appropriate matrix excipient to embed the nanoparticles is essential for the necessary disintegration and release of nanoparticles. In this context we investigated the influence of mannitol on the morphology, aerodynamic properties and disintegration behavior of nano-embedded microparticles. PLGA nanoparticles and mannitol were spray dried each as sole component and in combination in three different ratios. An influence of the mannitol content on the morphology was observed. Pure mannitol microparticles were solid and spherical, while the addition of nanoparticles resulted in raisin-shaped hollow particles. The different morphologies can be explained by diffusion processes of the compounds described by the Péclet-number. All powders showed suitable aerodynamic properties. By dispersion of the powders in simulated lung fluid, initial nanoparticle sizes could be recovered for samples containing mannitol. The fraction of redispersed nanoparticles was increased with increasing mannitol content. To evaluate the disintegration under conditions with higher comparability to the in vivo situation, spray-dried powders were exposed to >90% relative humidity. The disintegration behavior was monitored by analyzing roughness values by white light interferometry and supporting SEM imaging. The exposure to high relative humidity was shown to be sufficient for disintegration of the microparticles containing mannitol, releasing morphologically unchanged nanoparticles. With increasing mannitol content, the disintegration occurred faster and to a higher degree. Under these conditions, microparticles only composed of nanoparticles did not disintegrate. By enabling the release of nanoparticles from nano-embedded microparticles, mannitol was shown to be an ideal excipient to convert nanoparticles by spray drying into an inhalable dry power formulation.
DOI of the first publication: 10.1016/j.ejps.2017.04.003
URL of the first publication:
Link to this record: hdl:20.500.11880/27990
ISSN: 1879-0720
Date of registration: 1-Oct-2019
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Pharmazie
Professorship: NT - Prof. Dr. Marc Schneider
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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