Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425683
Title: Effects of particle surface modifications on dry powder formulation performances
Author: Schueller, Laurent Bruno
ISNI:       0000 0001 3556 7646
Awarding Body: University College London
Current Institution: University College London (University of London)
Date of Award: 2005
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Abstract:
Described in this dissertation are systematic studies designed to correlate the physico-chemical properties of dry powder inhalation formulations to the in vitro deposition patterns. Two model asthmatic drugs were selected for investigation: the hydrophilic β2 adrenoreceptor agonist, salbutamol sulphate (SS) and the hydrophobic synthetic steroid, beclomethasone dipropionate (BDP). To examine deposition differences between carrier particles from different sources, three different marketed grades of lactose were evaluated. In vitro assessment of the deposition using the Clickhaler®, as a device displayed significant differences depending on the carrier chosen. In particular BDP seemed to be positively influenced by the presence of fine lactose, whereas SS seemed to be more linked to the surface energetics of the coarse lactose. The influence played by the fines was further evaluated by using crystalline lactose/polyethylene glycol 4000 (PEG 4000 g mol-1) particles that were prepared by spray drying. Different parameters such as the chemical nature and the proportion of fines, the mixing sequence, and the drug to carrier ratio all influenced the deposition patterns of the drugs. Significant standardisation in the performances of BDP was achieved by modifying the surface of the coarse lactose. Improvements in SS deposition were also achieved using a new type of carrier surface modification. Partially amorphous lactose/PEG 4000 fines were allowed to crystallise onto air-jet sieved lactose surfaces. Parameters such as particle morphology and surface energetics appeared to play a key role in the drug deposition. PEG 4000 [45-90] μm was also studied as a probe carrier using the Aerolizer® This study also represented an opportunity to consider the device implication on the Twin Stage Impinger (TSI) deposition. Finally, the possibility of modifying the surface properties of the drug substance was investigated by a spray drying process. It was found by inverse gas chromatography (IGC) that PEG modified the surface energy parameters of the drug. Different solutions and suspensions were studied in order to generate crystalline particles with suitable properties for pulmonary administration.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.425683  DOI: Not available
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