Ampratwum, Esther; (2000) Characterisation and delivery of spray dried nedocromil sodium from a novel dry powder inhaler device. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

An ideal drug powder, for use in dry powder inhalers has particles in the respirable size range (<6 μm), which are not adhesive, cohesive or static. The particles should be stable in most atmospheric conditions, flow well and disperse readily from the liberation device. In this study, spray drying has been investigated as a means of controlling the particle size and morphology of nedocromil sodium and the effects of moisture on spray dried and milled powder assessed. The aerosol behaviour of both powders was evaluated in a new dry powder inhaler, under varying conditions of storage and testing. A 10% w/v aqueous solution of nedocromil sodium was spray dried using a Mini Büchi 190 spray dryer. Samples of milled and spray dried powder were exposed to varied relative humidities (0 to 98%) over a period of time. The thermal behaviour of the samples was studied using thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The surface morphology and size of the powders were examined by scanning electron microscopy (SEM) and laser diffraction. Isothermal calorimetry and dynamic vapour sorption were used to investigate the adsorption and desorption behaviour of both solids at room temperature. SEM micrographs indicated that the milled powder was apparently crystalline with particle agglomerates of approximately 5 μm mean size. Spray drying produced discrete, spherical particles in the size range 1 μm to 5 μm. Relative humidity had a marked effect on the physical stability of nedocromil sodium. The milled drug existed in different hydrate forms depending on relative humidity. The amorphous spray dried powder crystallised at humidities > 35%. The microcalorimetry and DVS data displayed different adsorption behaviour between the milled and spray dried powders, demonstrating that they may experience complicated moisture induced structural changes. Aerosol deposition studies showed that the milled drug-lactose blend aerosolised more efficiently from the delivery device than the spray dried drug-lactose blend. The milled formulation was significantly (p<0.05) affected by changing testing conditions only to 84% RH, or changing a combination of storage and testing conditions to 84% RH. However, the spray dried formulation showed no significant differences in delivery from the device regardless of changes in storage conditions, testing conditions or a combination of both.

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