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Open AccessArticle

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

School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK
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Academic Editors: Vjekoslav Štrukil and Matej Baláž
Molecules 2019, 24(21), 3990; https://doi.org/10.3390/molecules24213990
Received: 30 August 2019 / Revised: 29 October 2019 / Accepted: 30 October 2019 / Published: 5 November 2019
(This article belongs to the Special Issue Recent Development of Mechanochemical Synthesis)
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. View Full-Text
Keywords: formulation; cryo-milling; amorphous; co-amorphous; XRPD; DSC; ATR-FTIR; mechanochemistry formulation; cryo-milling; amorphous; co-amorphous; XRPD; DSC; ATR-FTIR; mechanochemistry
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MDPI and ACS Style

Elfakhri, R.; Burley, J.C. Investigation of Potential Amorphisation and Co-Amorphisation Behaviour of the Benzene Di-Carboxylic Acids upon Cryo-Milling. Molecules 2019, 24, 3990.

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