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Title: Characterisation of an amorphous dry powder aerosol system
Author: Venthoye, Maria Geraldine
ISNI:       0000 0001 3545 6305
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1997
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Amorphous spray dried powders of "respirable" size have been produced and their potential for use in powder aerosol formulations investigated. The drying conditions for salbutamol sulphate, a hydrophilic respiratory drug, were optimised using the Mini Büchi 190 spray dryer. The feed solution temperature and the location of the yield was found to influence the size and moisture content of the particles. The surface area and morphology were determined for the spray dried samples with comparisons made to micronised particles. The amorphous form is physically and thermodynamically unstable and under favourable temperature and relative humidity will revert back to the stable crystalline species. Various techniques were used to study this conversion and the appropriateness of further processing to induce aggregation. Microcalorimetry revealed; how different drying conditions would affect relative physical stability, the degree of batch to batch variation, and the influence of different carrier lactose types. Increased physical stability was imparted by the addition of amorphous spray dried lactose. In addition, the depression of glass transition temperature with moisture uptake was observed and the production of a partially crystalline form was detected. Aerosol deposition studies were carried out at 60.0 Lmin−1 with the Rotahaler® (Glaxo) using; the Andersen cascade impactor, multistage liquid and twin impingers. Deagglomeration and aerosolisation efficiency was inferred from device retention and oropharyngeal deposition. Respirable mass and fine particle dose indicated the likely degree of deep lung penetration. The impaction methods differed in the amount and reproducibility of the particle size information provided. Significant differences were detected in micronised samples but not in spray dried batches. At 28.3 Lmin−1 the Andersen was unable to adequately disperse and aerosolise the cohesive powders. Size enlargement into aggregates was achieved by tumbling carrier-free and drug/lactose mixes. The size fraction of carrier and the pre-storage humidity of drug significantly affected the measured aerosol properties.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Drug delivery systems