Masters Degrees (Clinical Pharmacology)

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Browsing Masters Degrees (Clinical Pharmacology) by Subject "Aerosols -- Therapeutic use"

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    Biophysical properties of experimental compositions of a synthetic pulmonary surfactant synsurf® for aerosolisation
    (Stellenbosch : Stellenbosch University, 2018-03) Agenbag, Chris-Mare; Van Zyl, Johann Martin; Smith, Johan; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine: Clinical Pharmacology.
    ENGLISH ABSTRACT: Synthetic pulmonary surfactant consists of phospholipid mixtures, free fatty acids and/or sterols, as well as specific protein constructs that mimic the functions of surfactant associated proteins B and/or C. Treatment of neonatal respiratory distress syndrome with surfactant replacement therapy consists of an invasive technique of endotracheal intubation and administration into the airway. For this reason, a less invasive approach such as nebulisation in these frail patients would be beneficial. Formulations of synthetic pulmonary surfactants intended for use, require that the in vitro-aerosolisation behaviour with regards to optimal particle size generation and conservation of surface tension, are ideal in order to maintain proper lung function. The objective of this study was to evaluate the suitability of different formulations of a new peptide-containing synthetic pulmonary surfactant Synsurf® during aerosolisation in comparison with the natural surfactants, Curosurf® (porcine) and Liposurf® (bovine). Synsurf®, was synthesised with and without alterations in key components that included cholesterol (1 % and 2 %), palmitic acid (11 %) and tripalmitin (7 %). An extrusion method through polycarbonate membranes with different pore sizes was also included during synthesis of the different formulations. Surfactants were aerosolised with the use of Aeroneb®Pro vibrating mesh nebuliser and particles generated were assessed with a Malvern Zetasizer® and visualised by scanning electron microscopy. Surface tension analyses was determined with a Drop Shape Analyser (DSA25). The main findings of this study showed that nebulisation of non-extruded Synsurf® formulations as well as Curosurf® and Liposurf®, produced a decrease of ± 80 % - 90 % in particle size, that is below the desired distribution range of 1 - 3 d.μm for inhaled particles. However, extrusion included in the synthesis of Synsurf®, generated larger particles post-nebulisation, within the desired range. Nebulisation also significantly influenced the density and viscosity of most Synsurf® preparations and natural surfactants. Additionally, an increase in cholesterol concentration showed a marked increase in viscosity of Synsurf®. With the exception of the original Synsurf® formulation, nebulisation diminished the surface tension lowering ability of all other surfactant preparations. Addition of palmitic acid/tripalmitin and 1 % cholesterol to the original Synsurf® formulation showed an overall pronounced reduction in surface tension in comparison to other formulations. In conclusion, the data of this study indicate that the original formulation of Synsurf® with addition of palmitic acid/tripalmitin and low concentrations of cholesterol, aid in the conservation of the surface tension properties and ideal particle size generation of the surfactant during nebulisation with a vibrating mesh nebuliser.