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Correlation of physicochemical properties of model drugs and aerosol deposition

de Oliveira, Ana Catarina Matos; (2009) Correlation of physicochemical properties of model drugs and aerosol deposition. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Dry powder inhalers (DPIs) are recognized devices for the administration of medicines to the lungs. Nevertheless, in general the effectiveness of these devices is poor generating respiratory depositions lower than 20%. The major reason for this occurrence is possibly related to the inter particulate forces between the drug and carrier components of a DPI formulation. The surface energy of the involved particles in these systems may be critical since it is implicated on the detachment mechanism among drug and carrier particles upon aerosolization. The aim of this thesis is to test the hypothesis that the adhesion between fine particles and the carrier should correlate with the surface energy, if the morphology of all samples is identical. To investigate this it was necessary to test the in vitro deposition of spherical particles with different surface energies assessed by Inverse Gas Chromatography (IGC) using the same carrier lactose and inhaler (Aerolizer®). A range of polymers and drugs were used to create spherical model "drugs" by spray drying and their deposition patterns were then investigated on the Twin Stage Impinger (TSI). Subsequent to the establishment of settings in the SDMicro™ Spray Dryer four model drugs were selected and reproducibly produced throughout namely. Polyacrylic Acid (PAA), Salbutamol Sulphate (SS), Polyvinyl Alcohol (PVA) and Polyvinyl Pyrrolidone (PVP). The morphology of the spray dried particles examined by Scanning Electron Microscopy (SEM) was shown to be correlated with the process parameters, principally the molecular weight of the material, nature of the solvent and inlet and outlet temperature. In particular, low molecular weight materials were more easily and reproducibly spray dried. Following a succession of preliminary experiments a method was established, in order to correlate the surface energy and Fine Particle Fraction (FPF) of the model drugs SS, PAA and PVA. It was possible to distinguish variations in intra and inter batch for the surface energy occurred by physical aging from a variety of model drugs. Moreover, even though the dispersive surface energy for the model drugs selected was very similar between the ranges 30-40 mJ/m2 a trend was achieved. In general, the FPF of the model drugs increased with decreasing surface energy and this may be related to a decrease on both the adhesion (drug-carrier/drug-device) and cohesion (drug-drug) of these particles hence presenting a superior in vitro deposition. However, no linear correlation between FPF and surface energy was reached with constant morphology suggesting that other factors apart from surface energy participate in the complex development of DPIs formulations.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Correlation of physicochemical properties of model drugs and aerosol deposition
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Aerosol; Deposition; Drugs; Physicochemical
URI: https://discovery.ucl.ac.uk/id/eprint/10105817
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