Investigations of a spray-drying method for producing nanoporous / nano-particulate microparticles (NPMPs) of proteins and protein-excipient composites
Citation:Orla Ní Ógáin, 'Investigations of a spray-drying method for producing nanoporous / nano-particulate microparticles (NPMPs) of proteins and protein-excipient composites', [thesis], Trinity College (Dublin, Ireland). School of Pharmacy & Pharmaceutical Sciences, 2009, pp 355
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The research, presented in this thesis, concerns the application of a spray-drying method to produce nanoporous/nano-particulate microparticles (NPMPs) of proteins, stabilising excipients and composites. The proposed method, involves spray-drying a solution or suspension of the compound(s) plus possibly a process enhancer (for example, ammonium carbonate) from a co-solvent system consisting of at least two volatile solvents. The potential of NPMPs for inclusion in dry powder formulations for pulmonary delivery of proteins or peptides was explored. Particles were visualised by scanning electron microscopy. Process stability was assessed by a selection of thermal analysis, solid-state characterisation (by powder x-ray diffraction), fourier transform infrared spectroscopy, SDS-PAGE and biological activity assays. Storage stability studies were also undertaken under different temperature and relative humidity conditions. Micromeritic characteristics of NPMPs, i.e., specific surface area, particle size, bulk and tapped densities were assessed. In-vitro deposition of powders was evaluated using an Andersen cascade impactor method. The model protein, lysozyme, was initially investigated and spray-dried as NPMPs from a feed system comprising methanol;water or ethanol:water co-solvent systems with ammonium carbonate or an alternative ammonium salt, as a process enhancer. Phase separation in the feed system, prior to spray-drying, was identified as a required step in the production of NPMPs of lysozyme from these systems. Particle morphology and NPMP production depended on the concentration and type of alcohol and process enhancer. Ethanol and ammonium carbonate were selected for further studies because less process enhancer was required to produce NPMPs with this combination and because ammonium carbonate has a low volatilisation temperature and was thus expected to be volatilised during the spray-drying method. Process stability investigations of NPMPs of lysozyme spray-dried from ethanol:water;ammonium carbonate systems suggested some perturbation in protein folding and secondary structure in the dried state. NPMPs showed excellent recovery of activity and secondary structure, however, on dissolution, suggesting that these were reversible perturbations. A series of mass ratio composite NPMPs of lysozymeitrehalose (9:1 - 1:1) and lysozyme:altemative excipient were spray-dried using an ethanol:water:ammonium carbonate feed system. All lysozyme composites studied also showed excellent retention of biological activity on dissolution.
Author: Ní Ógáin, Orla
Corrigan, Owen I.
Publisher:Trinity College (Dublin, Ireland). School of Pharmacy & Pharmaceutical Sciences
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Type of material:thesis
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