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Title: A supercritical carbon dioxide route to protein loaded microparticles for pulmonary drug delivery
Author: Vijayaraghavan, Meera
ISNI:       0000 0004 2747 3959
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2010
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In recent years, advances in biotechnology and molecular biology have produced many new protein and peptide based drugs. The pulmonary route potentially offers an efficient and convenient method of systemic drug delivery. One approach is to encapsulate the proteins or peptides into microparticles for more efficient administration. However, the sensitive nature of these molecules can result in their denaturation during traditional microparticle production techniques. The production of microparticles using supercritical carbon dioxide (SCC02) provides an attractive alternative, particularly the Particles from Gas Saturated Solutions (PGSS) method which uses scC02 to liquefy polymers and other excipients at physiological temperatures and in the absence of solvents. The overall aim of this work was to investigate the production of protein loaded microparticles with the optimum characteristics for pulmonary drug delivery using the PGSS technique. Preliminary investigations into suitable materials for particle production highlighted three classes of potentially useful materials; fatty acids, poly(ethylene glycol) (PEG) and PEG stearates. These materials showed a considerable depression in melting temperature in the presence of scC02, allowing microparticles of these materials to be prepared using a high pressure particle rig. The molecular weight of PEG and type of fatty acid used were discovered to have an effect on the size of the microparticles. The properties of PEG stearate microparticles were studied and found to be different from those made from corresponding mixtures of PEG and stearic acid. 11 Abstract Insulin was introduced as a model protein to microparticies consisting of myristic acid with PEG or PEG stearate. It was discovered that varying the concentration of myristic acid had an effect on the particie characteristics. The encapsulation efficiency of insulin was high and the release from the microparticies was complete within the first 10 minutes of the study. In vitro aerosolisation studies using a Next Generation Impactor were carried out to assess the aerodynamic properties of the insulin loaded microparticies. The final section of this thesis deals with extending the time over which this insulin was released from the microparticies prepared using the PGSS process. Poly(iactic acid) (PLA), a biodegradable polymer, was added to formulations containing myristic acid and PEG stearate. In order to facilitate the investigation, a mixture design and statistical software package were used. The addition of PLA was found to notably reduce the initial burst release of insulin from the microparticies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available