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Title: Supercritical CO2: a clean route to protein loaded microparticles
Author: Warren, Marie Georgiou
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2012
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Currently protein-based drugs are marketed almost exclusively for parenteral administration. Often this may require daily injections which are both painful and inconvenient to the patient, reducing compliance. The application of sustained release technology to proteins offers an improved route of delivery. This can be achieved by encapsulating the protein in a biodegradable polymer. Such systems will reduce the dosing frequency leading to a more efficacious and cost effective treatment. Encapsulating proteins into biodegradable polymers has been found to be promising for the delivery of proteins. Traditional encapsulation methods such as spray drying and emulsion techniques are unsuitable for proteins as they use heat and/or organic solvents, which can lead to the denaturing of the protein. This Thesis describes the use of a supercritical carbon dioxide (scC02) Particles from Gas Saturated Solutions (PGSS) route for the production of protein loaded microparticles. Initially, the performance of a particle production process based on the PGSS was investigated. It was found that post-expansion parameters heavily influence the particle properties in terms of particle yield, size and in vitro drug release. This allowed for the optimum processing conditions for generating the highest yield, smallest particle size and burst release to be identified. Moving on from this, the following chapter focuses on the particulate formulation by investigating the effect of blending different polymers to improve the particulate properties. Particles were produced from a base formulation of poly(1actic acid) (PLA) and poly(1actic-co-glycolic acid) (PLGA) blended with various excipients such as Poloxamer 407, poly(ethyl glycol) (PEG), poly(propylene glycol) (PPG) and a CO2-philic excipient PVAc-co-PVPi. It was found that increased miscibility of the excipients in the base formulation improves the compatabilisation of the protein and the polymer matrix, leading to a more homogeneous protein distribution in the polymer matrix. A more homogenous protein distribution within the microparticle was found to improve the in vitro release properties. The final chapter of this Thesis using a statistical Design of Experiment (DoE) approach to further investigate the effect of the excipient Poloxamer 407 when blended with PLA and PLGA. The formulation was optimised to produce a very small particle size of 31 f!m enabling successful injection through a target 25 G needle.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available