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Novel multi-component systems of propyphenazone and lonidamine: characterisation, physicochemical properties and quantum crystallography studies

Novel multi-component systems of propyphenazone and lonidamine: characterisation, physicochemical properties and quantum crystallography studies
Novel multi-component systems of propyphenazone and lonidamine: characterisation, physicochemical properties and quantum crystallography studies
This thesis reports novel multi-component systems of two APIs, PROPY and LON. Design and prediction strategies, tailored for each API, have been used to select appropriate co-former molecules used for subsequent screening and synthesis. Comprehensive characterisation of the products was followed by single crystal X-ray diffraction structural analysis and physicochemical property measurements. These include thermal properties, stability, dissolution and solubility which were characterised by DSC, TGA, PXRD and HPLC.

A subset of PROPY systems were selected to probe the nature of the API···co-former interactions. The experimental electron density distribution, based on very high resolution single crystal diffraction, was modelled and a topological analysis undertaken using Bader’s Atoms in Molecules (AIM) approach. Atomic charges, intermolecular interactions and their energies have been subsequently derived and compared between systems. Complementary theoretical calculations using the PIXEL and Crystal Explorer interaction energy approaches were undertaken and used to investigate the intermolecular interactions beyond atom···atom contacts. These permitted the decomposition of the intermolecular interactions into their constituent energy components for a comprehensive analysis. This novel approach provided new insight into the driving forces behind the formation of the solid state. Furthermore, this quantum crystallography approach enabled an analysis of the effect of the co-former on structure and the range of influencing factors that determine the physicochemical properties of these multi-component systems.
University of Southampton
Mapp, Lucy Kristina
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Mapp, Lucy Kristina
b90136ce-37b0-464a-8934-d44a8c2d7e48
Coles, Simon J.
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Mapp, Lucy Kristina (2017) Novel multi-component systems of propyphenazone and lonidamine: characterisation, physicochemical properties and quantum crystallography studies. University of Southampton, Doctoral Thesis, 481pp.

Record type: Thesis (Doctoral)

Abstract

This thesis reports novel multi-component systems of two APIs, PROPY and LON. Design and prediction strategies, tailored for each API, have been used to select appropriate co-former molecules used for subsequent screening and synthesis. Comprehensive characterisation of the products was followed by single crystal X-ray diffraction structural analysis and physicochemical property measurements. These include thermal properties, stability, dissolution and solubility which were characterised by DSC, TGA, PXRD and HPLC.

A subset of PROPY systems were selected to probe the nature of the API···co-former interactions. The experimental electron density distribution, based on very high resolution single crystal diffraction, was modelled and a topological analysis undertaken using Bader’s Atoms in Molecules (AIM) approach. Atomic charges, intermolecular interactions and their energies have been subsequently derived and compared between systems. Complementary theoretical calculations using the PIXEL and Crystal Explorer interaction energy approaches were undertaken and used to investigate the intermolecular interactions beyond atom···atom contacts. These permitted the decomposition of the intermolecular interactions into their constituent energy components for a comprehensive analysis. This novel approach provided new insight into the driving forces behind the formation of the solid state. Furthermore, this quantum crystallography approach enabled an analysis of the effect of the co-former on structure and the range of influencing factors that determine the physicochemical properties of these multi-component systems.

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Published date: September 2017

Identifiers

Local EPrints ID: 418007
URI: http://eprints.soton.ac.uk/id/eprint/418007
PURE UUID: 12875ef8-d471-4bb7-bc3a-54d5d09c5fa1
ORCID for Simon J. Coles: ORCID iD orcid.org/0000-0001-8414-9272

Catalogue record

Date deposited: 20 Feb 2018 17:30
Last modified: 29 Jan 2021 05:01

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Contributors

Author: Lucy Kristina Mapp
Thesis advisor: Simon J. Coles ORCID iD

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