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Title: Particle engineering of carriers for improved inhalation formulations of salbutamol sulphate
Author: Molina, Carlos
ISNI:       0000 0004 7960 9934
Awarding Body: University of Sussex
Current Institution: University of Sussex
Date of Award: 2019
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Particle engineering was used to modify particle morphology and the physicochemical/mechanical properties of carriers and active pharmaceutical ingredients. In this study, spray drying and crystallization were used as the main techniques for particle engineering; carriers included lactose, D-mannitol, and xylitol. L-leucine was used as an additive to modify the morphology of particles and salbutamol sulphate was used as an active pharmaceutical ingredient throughout the researched work. Engineered carriers were used, in some combination, in dry powder inhaler (DPI) formulations to determine whether or not there was an enhancement in the aerosolization performance of the engineered formulations. The prepared engineered carriers were analyzed using laser diffraction (particle size), differential scanning calorimetry (thermal behavior), scanning electron microscopy (morphology), powder X-ray diffraction (crystallinity), Fourier transform infrared spectroscopy (interaction at molecular level), powder flow characteristics (i.e. Carr's Index and angle of repose), high pressure liquid chromatography (HPLC), UV-vis spectroscopy, and in vitro aerosolization performance (deposition). It was determined that the efficacy, via Fine Particle Fraction (FPF), of the engineered spray dried lactose-leucine DPI formulation was improved from 25.51 ± 1.23% to 47.11 ± 9.94%. The performance of the engineered spray dried mannitol-leucine DPI formulation was also improved to 52.96 + 5.21%. The engineered spray dried mannitol-lactose-leucine DPI formulation had an aerosolization performance of 61.42 + 4.21%. The engineered xylitol crystals, however, had an aerosolization performance of 42.94 + 15.21% whereas the mannitol-lactose crystals had an aerosolization performance of 68.69 + 4.65%. Finally, the mannitol-salbutamol sulphate crystals had a fine particle fraction (FPF) of 62.53 + 6.84%. A physical mixture comparative study showed that it was better to engineer the carriers rather than use the commercially available carriers currently in the market. In addition, the results also showed that L-leucine acts as a lubricating agent when incorporated into the DPI formulations. Lastly, all of the engineered carriers showed some degree of agglomeration, which made coarse particles suitable for DPI formulations.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RS0192 Pharmaceutical technology ; TP0156.P3 Particle technology