Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.684338
Title: Factors affecting the stability of pharmaceutically relevant non-aqueous sols
Author: Mayes, Clare
ISNI:       0000 0004 5920 9060
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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Abstract:
The stability of pharmaceutical formulations in non-aqueous media is poorly understood. In order to discover which factors affect the stability, screening studies using a statistical Design of Experiment approach was adopted and revealed that; solid concentration, solvent, solid and surfactant types all have significant effects on the stability of the sol. In addition a number of factors, such as water concentration in combination with the solvent, were found be significant. The factors of water and then surfactant in combination with solvent and solid have been further investigated, by use of sedimentation, rheology and electrophoretic measurements. It was found that for hydrophilic pharmaceutical particles, water contamination had the largest impact on the sols' properties, particularly where the solvent had only limited water miscibility. The least impact was found with a hydrophobic particle and a water miscible solvent. In the absence of any water in the solvent, the anionic surfactant AOT was found to be an effective surfactant for most systems at stabilising the sols. Electrophoretic measurements revealed that the addition of AOT most cases reversed the charge of the particles to that observed in water. However, the surfactants 12-hydroxysteric acid and Brij-35 were found to be more effective than AOT at stabilising the systems against the effect of water contamination in the solvent. By addition of these surfactants it was possible to stop the catastrophic irreversible aggregation which resulted from water contamination. After the addition of surfactant, water had the effect of causing the suspensions to visibly thicken, but aggregation did not occur This study shows that the stabilisation of pharmaceutical dispersions is complex and there is no universal route to achieve this. However, for hydrophilic particles dispersed in a water immiscible non-polar solvent the effect of water in the solvent lead to aggregation of the particles, presumable due to capillary bridging effects; addition of a surfactant can help to mitigate these effects.
Supervisor: Luckham, Paul Sponsor: GlaxoSmithKline
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.684338  DOI: Not available
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