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

Abstract

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.

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.

Thesis embargoed until 31 December 2026.

Date of Award	Dec 2021
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Northern Ireland Department for the Economy, Science Foundation Ireland & National Science Foundation
Supervisor	Gavin Andrews (Supervisor) & Shu Li (Supervisor)