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Title: Atomisation, CO2 processing & injectability of polymers for drug delivery
Author: Whitaker, Mark A.
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2011
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Drug delivery via use of an injectable vehicle is investigated for controlled release formulations designed to reside in the body with the advantage of reducing patient discomfort by mitigating injection frequency. Fabrication of microparticles is undertaken from biocompatible polymers such as poly(DL-lactic-co-glycolic) acid (PLGA) and poly(DL-lactic) acid (PLA). These biopolymers provide an encapsulation matrix for a drug which is partially shielded from instant absorption and elimination when placed in the body. Over time these polymers degrade and the drug material that they are carrying is released in a sustained manner. The work presented in this Thesis has focussed on creating drug encapsulated microparticles using the properties of supercritical carbon dioxide (scC02). This has been achieved through the particles from gas saturated solutions (PGSS) technique, using scC02 as the plasticising component to mix biopolymers and drug material. Once blended the polymer mix is sprayed out through a nozzle, forming microparticles. PGSS performance is investigated though the optimisation of nozzle design. The comparison of orifice and gas assist nozzles is tested in order to quantify miroparticle size distributions that are of an acceptable size for injection. This has led to the construction of a new 2-fluid nozz1e rig. Different particle manufacture methods based on PGSS principles are also studied. Here ground biopolymers seeded with modelling drug have been re-plasticised in CO2 to create smooth hemispheres. The resulting injectable microparticles have shown sustained release after in vitro testing. Injection of polymeric microparticles is an overlooked step in the drug delivery process. Experience has shown that blockage of the syringe mechanism can be a problem under certain conditions, leading to poor control of the final product. Discrete Element Method (DEM) computer modelling is utilised in order to demonstrate that particle size distributions and shape are significant factors affecting blockages- showing good agreement with simulations.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available