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Molecular Dynamics and Physical Stability of Ibuprofen in Binary Mixtures with an Acetylated Derivative of Maltose

[Image: see text] In this paper, we explore the strategy increasingly used to improve the bioavailability of poorly water-soluble crystalline drugs by formulating their amorphous solid dispersions. We focus on the potential application of a low molecular weight excipient octaacetyl-maltose (acMAL) t...

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Autores principales: Grzybowska, Katarzyna, Grzybowski, Andrzej, Knapik-Kowalczuk, Justyna, Chmiel, Krzysztof, Woyna-Orlewicz, Krzysztof, Szafraniec-Szczęsny, Joanna, Antosik-Rogóż, Agata, Jachowicz, Renata, Kowalska-Szojda, Katarzyna, Lodowski, Piotr, Paluch, Marian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467776/
https://www.ncbi.nlm.nih.gov/pubmed/32584584
http://dx.doi.org/10.1021/acs.molpharmaceut.0c00517
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author Grzybowska, Katarzyna
Grzybowski, Andrzej
Knapik-Kowalczuk, Justyna
Chmiel, Krzysztof
Woyna-Orlewicz, Krzysztof
Szafraniec-Szczęsny, Joanna
Antosik-Rogóż, Agata
Jachowicz, Renata
Kowalska-Szojda, Katarzyna
Lodowski, Piotr
Paluch, Marian
author_facet Grzybowska, Katarzyna
Grzybowski, Andrzej
Knapik-Kowalczuk, Justyna
Chmiel, Krzysztof
Woyna-Orlewicz, Krzysztof
Szafraniec-Szczęsny, Joanna
Antosik-Rogóż, Agata
Jachowicz, Renata
Kowalska-Szojda, Katarzyna
Lodowski, Piotr
Paluch, Marian
author_sort Grzybowska, Katarzyna
collection PubMed
description [Image: see text] In this paper, we explore the strategy increasingly used to improve the bioavailability of poorly water-soluble crystalline drugs by formulating their amorphous solid dispersions. We focus on the potential application of a low molecular weight excipient octaacetyl-maltose (acMAL) to prepare physically stable amorphous solid dispersions with ibuprofen (IBU) aimed at enhancing water solubility of the drug compared to that of its crystalline counterpart. We thoroughly investigate global and local molecular dynamics, thermal properties, and physical stability of the IBU+acMAL binary systems by using broadband dielectric spectroscopy and differential scanning calorimetry as well as test their water solubility and dissolution rate. The obtained results are extensively discussed by analyzing several factors considered to affect the physical stability of amorphous systems, including those related to the global mobility, such as plasticization/antiplasticization effects, the activation energy, fragility parameter, and the number of dynamically correlated molecules as well as specific intermolecular interactions like hydrogen bonds, supporting the latter by density functional theory calculations. The observations made for the IBU+acMAL binary systems and drawn recommendations give a better insight into our understanding of molecular mechanisms governing the physical stability of amorphous solid dispersions.
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spelling pubmed-74677762020-09-03 Molecular Dynamics and Physical Stability of Ibuprofen in Binary Mixtures with an Acetylated Derivative of Maltose Grzybowska, Katarzyna Grzybowski, Andrzej Knapik-Kowalczuk, Justyna Chmiel, Krzysztof Woyna-Orlewicz, Krzysztof Szafraniec-Szczęsny, Joanna Antosik-Rogóż, Agata Jachowicz, Renata Kowalska-Szojda, Katarzyna Lodowski, Piotr Paluch, Marian Mol Pharm [Image: see text] In this paper, we explore the strategy increasingly used to improve the bioavailability of poorly water-soluble crystalline drugs by formulating their amorphous solid dispersions. We focus on the potential application of a low molecular weight excipient octaacetyl-maltose (acMAL) to prepare physically stable amorphous solid dispersions with ibuprofen (IBU) aimed at enhancing water solubility of the drug compared to that of its crystalline counterpart. We thoroughly investigate global and local molecular dynamics, thermal properties, and physical stability of the IBU+acMAL binary systems by using broadband dielectric spectroscopy and differential scanning calorimetry as well as test their water solubility and dissolution rate. The obtained results are extensively discussed by analyzing several factors considered to affect the physical stability of amorphous systems, including those related to the global mobility, such as plasticization/antiplasticization effects, the activation energy, fragility parameter, and the number of dynamically correlated molecules as well as specific intermolecular interactions like hydrogen bonds, supporting the latter by density functional theory calculations. The observations made for the IBU+acMAL binary systems and drawn recommendations give a better insight into our understanding of molecular mechanisms governing the physical stability of amorphous solid dispersions. American Chemical Society 2020-06-25 2020-08-03 /pmc/articles/PMC7467776/ /pubmed/32584584 http://dx.doi.org/10.1021/acs.molpharmaceut.0c00517 Text en Copyright © 2020 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Grzybowska, Katarzyna
Grzybowski, Andrzej
Knapik-Kowalczuk, Justyna
Chmiel, Krzysztof
Woyna-Orlewicz, Krzysztof
Szafraniec-Szczęsny, Joanna
Antosik-Rogóż, Agata
Jachowicz, Renata
Kowalska-Szojda, Katarzyna
Lodowski, Piotr
Paluch, Marian
Molecular Dynamics and Physical Stability of Ibuprofen in Binary Mixtures with an Acetylated Derivative of Maltose
title Molecular Dynamics and Physical Stability of Ibuprofen in Binary Mixtures with an Acetylated Derivative of Maltose
title_full Molecular Dynamics and Physical Stability of Ibuprofen in Binary Mixtures with an Acetylated Derivative of Maltose
title_fullStr Molecular Dynamics and Physical Stability of Ibuprofen in Binary Mixtures with an Acetylated Derivative of Maltose
title_full_unstemmed Molecular Dynamics and Physical Stability of Ibuprofen in Binary Mixtures with an Acetylated Derivative of Maltose
title_short Molecular Dynamics and Physical Stability of Ibuprofen in Binary Mixtures with an Acetylated Derivative of Maltose
title_sort molecular dynamics and physical stability of ibuprofen in binary mixtures with an acetylated derivative of maltose
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467776/
https://www.ncbi.nlm.nih.gov/pubmed/32584584
http://dx.doi.org/10.1021/acs.molpharmaceut.0c00517
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