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Mannitol Polymorphs as Carrier in DPIs Formulations: Isolation Characterization and Performance

The search for best performing carriers for dry powder inhalers is getting a great deal of interest to overcome the limitations posed by lactose. The aerosolization of adhesive mixtures between a carrier and a micronized drug is strongly influenced by the carrier solid-state properties. This work ai...

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Autores principales: Altay Benetti, Ayça, Bianchera, Annalisa, Buttini, Francesca, Bertocchi, Laura, Bettini, Ruggero
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401007/
https://www.ncbi.nlm.nih.gov/pubmed/34452073
http://dx.doi.org/10.3390/pharmaceutics13081113
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author Altay Benetti, Ayça
Bianchera, Annalisa
Buttini, Francesca
Bertocchi, Laura
Bettini, Ruggero
author_facet Altay Benetti, Ayça
Bianchera, Annalisa
Buttini, Francesca
Bertocchi, Laura
Bettini, Ruggero
author_sort Altay Benetti, Ayça
collection PubMed
description The search for best performing carriers for dry powder inhalers is getting a great deal of interest to overcome the limitations posed by lactose. The aerosolization of adhesive mixtures between a carrier and a micronized drug is strongly influenced by the carrier solid-state properties. This work aimed at crystallizing kinetically stable D-mannitol polymorphs and at investigating their aerosolization performance when used in adhesive mixtures with two model drugs (salbutamol sulphate, SS, and budesonide, BUD) using a median and median/high resistance inhaler. A further goal was to assess in vitro the cytocompatibility of the produced polymer-doped mannitol polymorphs toward two lung epithelial cell lines. Kinetically stable (up to 12 months under accelerate conditions) α, and δ mannitol forms were crystallized in the presence of 2% w/w PVA and 1% w/w PVP respectively. These solid phases were compared with the β form and lactose as references. The solid-state properties of crystallized mannitol significantly affected aerosolization behavior, with the δ form affording the worst fine particle fraction with both the hydrophilic (9.3 and 6.5%) and the lipophilic (19.6 and 32%) model drugs, while α and β forms behaved in the same manner (11–13% for SS; 53–58% for BUD) and better than lactose (8 and 13% for SS; 26 and 39% for BUD). Recrystallized mannitol, but also PVA and PVP, proved to be safe excipients toward lung cell lines. We concluded that, also for mannitol, the physicochemical properties stemming from different crystal structures represent a tool for modulating carrier-drug interaction and, in turn, aerosolization performance.
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spelling pubmed-84010072021-08-29 Mannitol Polymorphs as Carrier in DPIs Formulations: Isolation Characterization and Performance Altay Benetti, Ayça Bianchera, Annalisa Buttini, Francesca Bertocchi, Laura Bettini, Ruggero Pharmaceutics Article The search for best performing carriers for dry powder inhalers is getting a great deal of interest to overcome the limitations posed by lactose. The aerosolization of adhesive mixtures between a carrier and a micronized drug is strongly influenced by the carrier solid-state properties. This work aimed at crystallizing kinetically stable D-mannitol polymorphs and at investigating their aerosolization performance when used in adhesive mixtures with two model drugs (salbutamol sulphate, SS, and budesonide, BUD) using a median and median/high resistance inhaler. A further goal was to assess in vitro the cytocompatibility of the produced polymer-doped mannitol polymorphs toward two lung epithelial cell lines. Kinetically stable (up to 12 months under accelerate conditions) α, and δ mannitol forms were crystallized in the presence of 2% w/w PVA and 1% w/w PVP respectively. These solid phases were compared with the β form and lactose as references. The solid-state properties of crystallized mannitol significantly affected aerosolization behavior, with the δ form affording the worst fine particle fraction with both the hydrophilic (9.3 and 6.5%) and the lipophilic (19.6 and 32%) model drugs, while α and β forms behaved in the same manner (11–13% for SS; 53–58% for BUD) and better than lactose (8 and 13% for SS; 26 and 39% for BUD). Recrystallized mannitol, but also PVA and PVP, proved to be safe excipients toward lung cell lines. We concluded that, also for mannitol, the physicochemical properties stemming from different crystal structures represent a tool for modulating carrier-drug interaction and, in turn, aerosolization performance. MDPI 2021-07-21 /pmc/articles/PMC8401007/ /pubmed/34452073 http://dx.doi.org/10.3390/pharmaceutics13081113 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Altay Benetti, Ayça
Bianchera, Annalisa
Buttini, Francesca
Bertocchi, Laura
Bettini, Ruggero
Mannitol Polymorphs as Carrier in DPIs Formulations: Isolation Characterization and Performance
title Mannitol Polymorphs as Carrier in DPIs Formulations: Isolation Characterization and Performance
title_full Mannitol Polymorphs as Carrier in DPIs Formulations: Isolation Characterization and Performance
title_fullStr Mannitol Polymorphs as Carrier in DPIs Formulations: Isolation Characterization and Performance
title_full_unstemmed Mannitol Polymorphs as Carrier in DPIs Formulations: Isolation Characterization and Performance
title_short Mannitol Polymorphs as Carrier in DPIs Formulations: Isolation Characterization and Performance
title_sort mannitol polymorphs as carrier in dpis formulations: isolation characterization and performance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401007/
https://www.ncbi.nlm.nih.gov/pubmed/34452073
http://dx.doi.org/10.3390/pharmaceutics13081113
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