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Investigation of Potential Amorphisation and Co-Amorphisation Behaviour of the Benzene Di-Carboxylic Acids upon Cryo-Milling

Multi-component formulations offer a way to modulate the physico-chemical properties of drug molecules and thereby enhance their efficacy as medicines compared to using only the raw drug, with mechano-chemical synthesis being an increasingly popular way to create these novel materials in a research...

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Detalles Bibliográficos
Autores principales: Elfakhri, Rehab, Burley, Jonathan C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865180/
https://www.ncbi.nlm.nih.gov/pubmed/31694147
http://dx.doi.org/10.3390/molecules24213990
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author Elfakhri, Rehab
Burley, Jonathan C.
author_facet Elfakhri, Rehab
Burley, Jonathan C.
author_sort Elfakhri, Rehab
collection PubMed
description Multi-component formulations offer a way to modulate the physico-chemical properties of drug molecules and thereby enhance their efficacy as medicines compared to using only the raw drug, with mechano-chemical synthesis being an increasingly popular way to create these novel materials in a research setting. However, to date studies have focussed on employing pharmaceutically acceptable components, which has led to the literature featuring chemically diverse pairings of drug and excipient. Here we investigate the outcome of cryo-milling and co-cryo-milling of a series of three simple geometrical isomers of benzene di-carboxylic acid with a view to developing a chemically simple model system to investigate areas including cryo-milling, co-cryo-milling, co-amorphous formulation, etc. All three single-component materials exhibit differing behaviour upon cryo-milling and subsequent storage, as do the two-component mixtures. The surprisingly differing behaviours of these chemically similar species upon cryo-milling and co-cryo-milling suggest that molecular chemistry may not be the dominant influence on the outcome of mechano-chemical syntheses, and that other properties should be explored to develop a predictive model for the outcomes of these types of reactions.
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spelling pubmed-68651802019-12-09 Investigation of Potential Amorphisation and Co-Amorphisation Behaviour of the Benzene Di-Carboxylic Acids upon Cryo-Milling Elfakhri, Rehab Burley, Jonathan C. Molecules Article Multi-component formulations offer a way to modulate the physico-chemical properties of drug molecules and thereby enhance their efficacy as medicines compared to using only the raw drug, with mechano-chemical synthesis being an increasingly popular way to create these novel materials in a research setting. However, to date studies have focussed on employing pharmaceutically acceptable components, which has led to the literature featuring chemically diverse pairings of drug and excipient. Here we investigate the outcome of cryo-milling and co-cryo-milling of a series of three simple geometrical isomers of benzene di-carboxylic acid with a view to developing a chemically simple model system to investigate areas including cryo-milling, co-cryo-milling, co-amorphous formulation, etc. All three single-component materials exhibit differing behaviour upon cryo-milling and subsequent storage, as do the two-component mixtures. The surprisingly differing behaviours of these chemically similar species upon cryo-milling and co-cryo-milling suggest that molecular chemistry may not be the dominant influence on the outcome of mechano-chemical syntheses, and that other properties should be explored to develop a predictive model for the outcomes of these types of reactions. MDPI 2019-11-05 /pmc/articles/PMC6865180/ /pubmed/31694147 http://dx.doi.org/10.3390/molecules24213990 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Elfakhri, Rehab
Burley, Jonathan C.
Investigation of Potential Amorphisation and Co-Amorphisation Behaviour of the Benzene Di-Carboxylic Acids upon Cryo-Milling
title Investigation of Potential Amorphisation and Co-Amorphisation Behaviour of the Benzene Di-Carboxylic Acids upon Cryo-Milling
title_full Investigation of Potential Amorphisation and Co-Amorphisation Behaviour of the Benzene Di-Carboxylic Acids upon Cryo-Milling
title_fullStr Investigation of Potential Amorphisation and Co-Amorphisation Behaviour of the Benzene Di-Carboxylic Acids upon Cryo-Milling
title_full_unstemmed Investigation of Potential Amorphisation and Co-Amorphisation Behaviour of the Benzene Di-Carboxylic Acids upon Cryo-Milling
title_short Investigation of Potential Amorphisation and Co-Amorphisation Behaviour of the Benzene Di-Carboxylic Acids upon Cryo-Milling
title_sort investigation of potential amorphisation and co-amorphisation behaviour of the benzene di-carboxylic acids upon cryo-milling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865180/
https://www.ncbi.nlm.nih.gov/pubmed/31694147
http://dx.doi.org/10.3390/molecules24213990
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