Al-Hadithi, Dima N.; (2004) Carrier surface modifications to improve aerosol performance of dry powder inhalation delivery. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

Particulate inhalation carriers are an important means of drug delivery to the respiratory tract, with a great potential for improving current therapies. This thesis set out to investigate the hypothesis that physical and chemical changes to particulate inhalation carriers can modify their surface interactions with asthma drugs leading to improved dry powder inhalation therapy. A variety of materials were used as carriers for two model drugs (salbutamol sulphate and beclomethasone dipropionate). Key parameters studied were aerosol drug deposition, surfece energy, charging and amorphous content. Amorphous carrier blends containing a coarse lactose carrier blended with amorphous lactose fines (10 % w/w of coarse carrier) were crystallised at 53 % RH for varying lengths of time. Significant improvements in the deposition of salbutamol sulphate were demonstrated by using a 2 hour surface crystallised lactose carrier. Differences in carrier performance were attributed to changes in surface crystallinity and, more directly, by modifications of particle morphology, charging behaviour and surface energetics. Improvements in salbutamol sulphate deposition were also achieved using α-D-glucose as a carrier. For BDP, significant improvements in fine particle fractions were demonstrated using peracetylated derivatives of α or β- D-glucose, lactose and cellulose as model carriers; with particle morphology and surface energy being key factors affecting drug deposition. A series of novel model carriers were produced by chemical derivatisation of commercial polystyrene based polymer beads. Changes in dispersive energy of the beads were found to correlate well with salbutamol sulphate deposition. By examining the complex interactions of particulate formulations, substantial improvements in deposition were achieved by carrier modifications. However, there was no one factor that dominated performance, but rather a combination of effects related to surface energy, charge and morphology.

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