Continuous manufacture of enabling formulations for a poorly soluble compound using hot melt extrusion technology

Over the past few decades, hot melt extrusion has emerged as a tremendously useful and versatile technology within pharmaceutical research and development. As a well-established technique in the production of oral solid dosage formulations, its operating capacity has the capability to address formulation and manufacturing issues associated with drugs which possess poor solubility, permeability and bioavailability. With traditional, batch-style manufacturing methods dominating the industrial production of oral solid dosage forms, and the associated high costs arising from its non-continuous processing structure and inefficiency, the industry welcomes ideas which generate increased efficiency and cost-effectiveness. A concept which hot melt extrusion processing embodies.<br/><br/>The work presented in this thesis sought to further investigate the use of hot melt extrusion as a platform to manufacture enabling formulations i.e., formulations which can help make drugs bioavailable, using model small molecule compounds. Furthermore, the focus on issues which arise during processing of thermally labile drugs using hot melt extrusion technology have been examined. This technology was maximised and tested as alternative processing conditions were explored in an attempt to overcome this hurdle and allow a larger population of drugs to be processed, encompassing those possessing poor thermal stability. To that end, hydrochlorothiazide and meloxicam were used as model compounds, both selected by their distinguishing properties; exhibiting poor solubility with high melting points and thermal lability. Hydrochlorothiazide was prepared in cocrystal and coamorphous forms using hot melt extrusion in chapters 2-4, and meloxicam was prepared as a polymer amorphous solid dispersion in chapter 5, also using hot melt extrusion.<br/><i><br/>Thesis embargoed until 31 December 2026</i>.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

Queen's University Belfast

Year dc:date.issued

2021

Author dc:creator

• Lagan, Colette

Advisors dc:contributor.advisor

• Andrews, Gavin
• Li, Shu

Language dc:language

eng

Identifier

oai:pure.qub.ac.uk/portal:studenttheses/ea8d602a-1140-445a-a47c-701bc715c6de

OAI identifier oai:identifier

oai:pure.qub.ac.uk/portal:studenttheses/ea8d602a-1140-445a-a47c-701bc715c6de