{"id":{"repo_id":"east-anglia","oai_identifier":"oai:ueaeprints.uea.ac.uk:56823"},"canonical_url":"https://search.dev.ndltd.org/etd/east-anglia/oai:ueaeprints.uea.ac.uk:56823","repository":{"repo_id":"east-anglia","name":"University of East Anglia","base_url":"https://ueaeprints.uea.ac.uk/cgi/oai2"},"display":{"title":"Polymer drug dispersions: understanding structure and dynamics","abstract":"Poor physical stability is a limiting factor in the pharmaceutical development of APIs. Amorphous drugs are attractive due to increased dissolution; however can unpredictably revert to the thermodynamically stable crystalline form. Accurate prediction of molecular level physical stability would be advantageous. Research surrounding stability prediction is evolving; but challenging, including thermodynamic, molecular and kinetic factors. This study focussed on gaining a molecular level understanding of the structure and dynamics of amorphous dispersions using three model drugs. We aimed to develop solid-state NMR methods to provide invaluable information on molecular mobility; to ultimately use NMR for the prediction of crystallisation outcomes from stability studies, leading to quicker prediction of potential storage issues, since mobility is a key factor a�ecting stability in the amorphous state. VT solid-state NMR was used to probe di�erences in local mobility between drug and polymer; and to monitor polymorphic transitions/crystallisation in high loaded dispersions. Methodologies were veri�ed using additional physicochemical approaches. We demonstrated: • Di�erences in local mobility of drug/polymer dependent on model system and drug loading. • Miscibility detection down to 2 nm, including important temperature dependent observations. VT relaxation curves could become important visual tools for quanti�cation of drug loading and prediction of miscibility during initial development. • VT NMR was a useful tool for quick and accurate prediction of high temperature stability study outcomes • Insight into crystallisation of pharmaceuticals in formulation, demonstrating mapping complex phase transitions in high loaded dispersions • Detection of di�erent dynamic features of tolbutamide, including the identi�cation of motional processes responsible for the detection of its structural transitions VT solid-state NMR has provided a signi�cant quantity of data surrounding the mobility and stability of our systems of study. These methods provide us with a valuable characterisation `toolkit' for probing molecular mobility in solid dispersions, therefore aiding the prediction of potential long term stability issues.","abstract_html":"Poor physical stability is a limiting factor in the pharmaceutical development of APIs. Amorphous drugs are attractive due to increased dissolution; however can unpredictably revert to the thermodynamically stable crystalline form. Accurate prediction of molecular level physical stability would be advantageous. Research surrounding stability prediction is evolving; but challenging, including thermodynamic, molecular and kinetic factors. This study focussed on gaining a molecular level understanding of the structure and dynamics of amorphous dispersions using three model drugs. We aimed to develop solid-state NMR methods to provide invaluable information on molecular mobility; to ultimately use NMR for the prediction of crystallisation outcomes from stability studies, leading to quicker prediction of potential storage issues, since mobility is a key factor a�ecting stability in the amorphous state. VT solid-state NMR was used to probe di�erences in local mobility between drug and polymer; and to monitor polymorphic transitions/crystallisation in high loaded dispersions. Methodologies were veri�ed using additional physicochemical approaches. We demonstrated: • Di�erences in local mobility of drug/polymer dependent on model system and drug loading. • Miscibility detection down to 2 nm, including important temperature dependent observations. VT relaxation curves could become important visual tools for quanti�cation of drug loading and prediction of miscibility during initial development. • VT NMR was a useful tool for quick and accurate prediction of high temperature stability study outcomes • Insight into crystallisation of pharmaceuticals in formulation, demonstrating mapping complex phase transitions in high loaded dispersions • Detection of di�erent dynamic features of tolbutamide, including the identi�cation of motional processes responsible for the detection of its structural transitions VT solid-state NMR has provided a signi�cant quantity of data surrounding the mobility and stability of our systems of study. These methods provide us with a valuable characterisation `toolkit' for probing molecular mobility in solid dispersions, therefore aiding the prediction of potential long term stability issues.","abstract_has_math":false,"creators":["Hawarden, Lucy Elizabeth"],"institution":"University of East Anglia","degree_name":"phd","degree_level":"doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-04","date_published":"2015-04","updated_at":"2026-07-24T02:12:10Z","subjects":[],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Hawarden, Lucy Elizabeth"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2015-04"]},{"key":"dc:date.issued","label":"Date","values":["2015-04"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["School of Pharmacy"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of East Anglia"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://ueaeprints.uea.ac.uk/id/eprint/56823/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["phd"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://ueaeprints.uea.ac.uk/id/eprint/56823/1/Lucy_Hawarden_Polymer_drug_dispersions_understanding_structure_and_dynamics_2015.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Poor physical stability is a limiting factor in the pharmaceutical development of APIs. Amorphous drugs are attractive due to increased dissolution; however can unpredictably revert to the thermodynamically stable crystalline form. Accurate prediction of molecular level physical stability would be advantageous. Research surrounding stability prediction is evolving; but challenging, including thermodynamic, molecular and kinetic factors. This study focussed on gaining a molecular level understanding of the structure and dynamics of amorphous dispersions using three model drugs. We aimed to develop solid-state NMR methods to provide invaluable information on molecular mobility; to ultimately use NMR for the prediction of crystallisation outcomes from stability studies, leading to quicker prediction of potential storage issues, since mobility is a key factor a�ecting stability in the amorphous state. VT solid-state NMR was used to probe di�erences in local mobility between drug and polymer; and to monitor polymorphic transitions/crystallisation in high loaded dispersions. Methodologies were veri�ed using additional physicochemical approaches. We demonstrated: • Di�erences in local mobility of drug/polymer dependent on model system and drug loading. • Miscibility detection down to 2 nm, including important temperature dependent observations. VT relaxation curves could become important visual tools for quanti�cation of drug loading and prediction of miscibility during initial development. • VT NMR was a useful tool for quick and accurate prediction of high temperature stability study outcomes • Insight into crystallisation of pharmaceuticals in formulation, demonstrating mapping complex phase transitions in high loaded dispersions • Detection of di�erent dynamic features of tolbutamide, including the identi�cation of motional processes responsible for the detection of its structural transitions VT solid-state NMR has provided a signi�cant quantity of data surrounding the mobility and stability of our systems of study. These methods provide us with a valuable characterisation `toolkit' for probing molecular mobility in solid dispersions, therefore aiding the prediction of potential long term stability issues."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Polymer drug dispersions: understanding structure and dynamics"]}]}],"canonical_facts":{"dc:creator":["Hawarden, Lucy Elizabeth"],"dc:date":["2015-04"],"dc:date.issued":["2015-04"],"dc:description.abstract":["Poor physical stability is a limiting factor in the pharmaceutical development of APIs. Amorphous drugs are attractive due to increased dissolution; however can unpredictably revert to the thermodynamically stable crystalline form. Accurate prediction of molecular level physical stability would be advantageous. Research surrounding stability prediction is evolving; but challenging, including thermodynamic, molecular and kinetic factors. This study focussed on gaining a molecular level understanding of the structure and dynamics of amorphous dispersions using three model drugs. We aimed to develop solid-state NMR methods to provide invaluable information on molecular mobility; to ultimately use NMR for the prediction of crystallisation outcomes from stability studies, leading to quicker prediction of potential storage issues, since mobility is a key factor a�ecting stability in the amorphous state. VT solid-state NMR was used to probe di�erences in local mobility between drug and polymer; and to monitor polymorphic transitions/crystallisation in high loaded dispersions. Methodologies were veri�ed using additional physicochemical approaches. We demonstrated: • Di�erences in local mobility of drug/polymer dependent on model system and drug loading. • Miscibility detection down to 2 nm, including important temperature dependent observations. VT relaxation curves could become important visual tools for quanti�cation of drug loading and prediction of miscibility during initial development. • VT NMR was a useful tool for quick and accurate prediction of high temperature stability study outcomes • Insight into crystallisation of pharmaceuticals in formulation, demonstrating mapping complex phase transitions in high loaded dispersions • Detection of di�erent dynamic features of tolbutamide, including the identi�cation of motional processes responsible for the detection of its structural transitions VT solid-state NMR has provided a signi�cant quantity of data surrounding the mobility and stability of our systems of study. These methods provide us with a valuable characterisation `toolkit' for probing molecular mobility in solid dispersions, therefore aiding the prediction of potential long term stability issues."],"dc:format":["application/pdf"],"dc:identifier.uri":["https://ueaeprints.uea.ac.uk/id/eprint/56823/1/Lucy_Hawarden_Polymer_drug_dispersions_understanding_structure_and_dynamics_2015.pdf"],"dc:language":["en"],"dc:publisher.department":["School of Pharmacy"],"dc:publisher.institution":["University of East Anglia"],"dc:relation.isreferencedby":["https://ueaeprints.uea.ac.uk/id/eprint/56823/"],"dc:title":["Polymer drug dispersions: understanding structure and dynamics"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["phd"]},"updated_at":"2026-07-24T02:12:10Z"}