Ibrahim, SF, Pickering, J, Ramachandran, V et al. (1 more author) (2022) Prediction of the Mechanical Deformation Properties of Organic Crystals Based upon their Crystallographic Structures: Case Studies of Pentaerythritol and Pentaerythritol Tetranitrate. Pharmaceutical Research, 39 (12). pp. 3063-3078. ISSN 0724-8741
Abstract
Purpose
Development of a quantitative model and associated workflow for predicting the mechanical deformation properties (plastic deformation or cleavage fracture) of organic single crystals from their crystallographic structures using molecular and crystallographic modelling.
Methods
Intermolecular synthons, hydrogen bonding, crystal morphology and surface chemistry are modelled using empirical force fields with the data integrated into the analysis of lattice deformation as computed using a statistical approach.
Results
The approach developed comprises three main components. Firstly, the identification of the likely direction of deformation based on lattice unit cell geometry; secondly, the identification of likely lattice planes for deformation through the calculation of the strength and stereochemistry of interplanar intermolecular interactions, surface plane rugosity and surface energy; thirdly, identification of potential crystal planes for cleavage fracture by assessing intermolecular bonding anisotropy. Pentaerythritol is predicted to fracture by brittle cleavage on the {001} lattice planes by strong in-plane hydrogen-bond interactions in the <110>, whereas pentaerythritol tetranitrate is predicted to deform by plastic deformation through the slip system {110} < 001>, with both predictions being in excellent agreement with known experimental data.
Conclusion
A crystallographic framework and associated workflow for predicting the mechanical deformation of molecular crystals is developed through quantitative assessment of lattice energetics, crystal surface chemistry and crystal defects. The potential for the de novo prediction of the mechanical deformation of pharmaceutical materials using this approach is highlighted for its potential importance in the design of formulated drug products process as needed for manufacture by direct compression.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. This is an author produced version of an article, published in Pharmaceutical Research. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | crystallographic modelling; elastic anisotropy; mechanical properties; slip planes; synthonic engineering |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemical & Process Engineering (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 21 Jul 2022 14:29 |
Last Modified: | 01 Jul 2023 00:13 |
Status: | Published |
Publisher: | Springer |
Identification Number: | 10.1007/s11095-022-03314-x |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:189220 |