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Title: Engineering excipient-free particles for inhalation
Author: Mueannoom, W.
ISNI:       0000 0004 5362 1265
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2014
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The size of inhalable particles should be approximately between 1-5 µm to be delivered to the lower respiratory tract. However, there are some disadvantages of the powders having such a small particle size, such as the difficulty of aerosolisation due to their intrinsic cohesiveness. Generating porous particles is a way of increasing the physical size of particles to enable effective aerosolisation but remain sufficiently small to reach the lower airways. A modified Hewlett-Packard thermal inkjet printer (TIJ) and airbrush (Model 200-3, USA) were used to engineer drug solutions of the inhalable drugs salbutamol sulphate (SS) and combination particles of beclometasone dipropionate (BDP) and SS (drug-drug particles). Subsequently, L-leucine was added with the aim of improving dispersibility and aerosol performance of SS and BDP:SS particles. The results demonstrated that the spray freeze dried (SFD) particles produced from both techniques had a low density of less than 0.1 g/cm3, and were spherical and porous. The SFD SS was amorphous; whereas, the inclusion of either L-leucine or BDP in formulations produced particles exhibiting partial crystallinity. This led to an enhancement of the BDP release from the SFD BDP:SS particles in the dissolution study due to: a) the largely amorphous nature of the particles b) SS acting as a solubility enhancer and c) the high surface area of the porous structure, compared to Easyhaler® Beclometasone. The SFD particles produced by the airbrush had a smaller physical size (ca: 4-10 µm) than those from the TIJ (ca: 5-30 µm). Next generation impactor (NGI) analysis indicated that the particles sprayed from the airbrush had a smaller aerodynamic size (MMAD; 0.5-5 µm) and higher fine particle fraction (FPF) (47.8-70.8 % FPF) than those particles jetted by the TIJ. In addition, engineering the combined particles of BDP:SS using the TIJ and airbrush proved that homogeneity of the drugs was achieved due to the equality of the drugs’ deposition in each NGI stage (p > 0.05). The presence of L-leucine enhanced the dispersibility of the SFD particles as the L-leucine content was increased, due to enrichment with L-leucine on the particle’s surface, and this led to a high percentage FPF being obtained. Spray freeze-drying using the TIJ and airbrush requires only a small volume of the drug solution (approximately < 5 mL for TIJ and 5-20 mL for the airbrush), which means the potential for pulmonary formulation can be assessed early in the preformulation stage.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available