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Spray drying as a method for fabrication of particulate pulmonary delivery systems

Kandil, Amr Essam; (2006) Spray drying as a method for fabrication of particulate pulmonary delivery systems. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

The interest in the pulmonary route as a delivery port for peptides and proteins has emerged new opportunities for improved and innovative drug delivery systems. The use of spray drying as a formulation technique for pulmonary delivery systems can extend their capabilities in terms of stability, reproducibility and efficacy. Spray drying offers a fast and efficient approach to the generation of dry, potentially respirable powders through one step process. This can be applied to solutions, suspensions and emulsions, atomised as a fine spray into a hot drying medium to produce a dry particulate powder. This thesis describes an investigation into the influence of formulation components and spray drying parameters on the resulting powder characteristics prepared using a modified double emulsion spray drying method. The effects of spray drying parameters (pump speed, aspirator level, heat control level, feed concentration) and formulation excipients (polyvinylpolypyrrolidone (PVP), polyvinyl alcohol (PVA), tocopheryl polyethylene glycol 1000 succinate (vitamin ETPGS), polysorbate 20 (tween 20), lactose) on ovalbumin loaded in polymeric poly (lactide-co-glycolide) (PLGA) were preliminarily investigated. A modified double emulsion spray drying method was optimised, in terms of microparticle size, morphology, percentage yield, ovalbumin loading and in vitro deposition capability. Using lactose in the external aqueous phase within the emulsification process was seen to produce high yield of spherical microparticles with particle size below 6μm, with narrow size distribution and hence suitable for inhalation. These microparticles showed high ovalbumin loading efficiency and promising in vitro deposition using both an air jet nebuliser and rotahaler. The same modified method using different lactose concentrations was investigated using insulin as fragile model protein. The method demonstrated successful insulin encapsulation displaying optimal release and aerosolisation properties, and would be predicted to exhibit high deposition in the lower regions of the respiratory tract, thereby facilitating systemic delivery. The use of polyethyleneimine (PEI) as an agent in the formulation of cationic microparticles using modified double emulsion spray drying method as a novel approach was investigated. PEI concentrations had an effect on the surface charge, morphology and size distribution. These positively charged microparticles showed a high DNA loading efficiency and the formation of a stable complex with adequate respirable characteristics. Preliminary data on the in vivo application of these cationic microparticles using hepatitis B plasmid showed higher immunological responses compared with free plasmid in mice.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Spray drying as a method for fabrication of particulate pulmonary delivery systems
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Delivery; Drying; Fabrication; Particulate; Pulmonary; Spray
URI: https://discovery.ucl.ac.uk/id/eprint/10119454
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