Development of the twin-screw extrusion platform for the manufacture of a liposomal formulation in a single-step, solvet-free and continuous process

Abstract

The overarching aim of this thesis was to develop a novel manufacturing platform for a liposomal/proliposomal formulation, through the use of twin-screw extrusion (TSE). This would be beneficial as current liposomal formulations suffer from a number of drawbacks, namely poor stability of liposomal suspensions and the complex manufacturing process. To overcome these drawbacks, selection and understanding of the necessary formulation components was first obtained. Thermal screening techniques alongside Flory-Huggins Theory was used to achieve this. Following this, an understanding of the system was gathered using a combination of thermal, microscopic and rheological techniques. It was demonstrated for the first time a proliposomal powder could be produced via TSE and upon reconstitution gave a liposomal suspension. Several drug loaded formulations were then manufactured and provided an insight to specific critical quality attributes and how they could be tailored by manipulation of formulation and process parameters. Finally, the potential of the system was demonstrated using insulin as a model biologic compound and provided potential avenues for further work. In summary, this thesis demonstrated a novel manufacturing technique for liposomal nanoparticle formulations using TSE. The process was a single-step, solvent free and continuous process overcoming the drawbacks of current manufacturing techniques.

Thesis embargoed until 31 December 2027

Date of Award	Dec 2022
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) & Justin Tian (Supervisor)