Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747398
Title: Studying phase transitions and co-crystallisation in pharmaceutical materials
Author: Clout, A. E.
ISNI:       0000 0004 7230 4257
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
Abstract:
For a drug to be effective it must be in solution so that it can be absorbed by the body at the site of action. Therefore, it must be soluble in an aqueous environment. For practical reasons many drugs are formulated in the solid state; an understanding of how the drug transitions from solid to solution is hence critical. The two key factors to be considered are the drug’s solubility and dissolution rate. In this work a novel method for the analysis of phase transitions in pharmaceutical materials was developed by combining high energy synchrotron X-ray diffraction with differential scanning calorimetry (DSC-XRD). This was used to collect in situ structural and calorimetric data on temperature driven phase transitions. Initial work was carried out to prove the utility of the technique by examining two enantiotropically polymorphic systems, and subsequently it was used to examine phase transitions in materials exhibiting multiple polymorphs. Building on this, the effect of sugar based excipients on the crystallisation behaviour of paracetamol glasses upon heating was examined, with particular emphasis on the stabilisation of metastable polymorphs II and III. DSC-XRD was further employed in the production of new co-crystals between isonicotinamide and three antioxidant compounds. The ability of four different techniques (solvent evaporation, thermal inkjet printing, heating, and milling) to prepare these co-crystals was investigated in detail. Finally, physical vapour deposition, a novel technique in the field of pharmaceuticals, was investigated for the preparation of amorphous materials, with particular emphasis on drugs considered to be poor glass formers. DSC-XRD has been demonstrated to be an incredibly powerful tool for the analysis of phase transitions and co-crystallisation in pharmaceutical materials, and physical vapour deposition has been shown to have great potential for preparing amorphous drugs from poor glass formers.
Supervisor: Williams, G. ; Gaisford, S. ; Salzmann, C. G. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.747398  DOI: Not available
Share: