Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.513535
Title: The role of surface properties in the high shear granulation of pharmaceuticals
Author: Ho, Raimundo
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2010
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Abstract:
This thesis presents a detailed study into the role of surface chemistry in the high shear granulation of organic pharmaceutical solids. Crystalline materials with markedly different surface chemistries were selected as model compounds which were granulated with a polymeric binder. The surface wettability of primary powders was evaluated by employing the sessile drop contact angle measurements to evaluate the facet-specific surface energetics of macroscopic crystals, obtained via a solvent-mediated or a temperature-controlled crystallisation technique. A novel methodology using inverse gas chromatography (IGC) at finite concentrations (FC) was developed to evaluate surface energy distributions of the powder samples. The surface energetics of organic macroscopic crystals was found to be facet-specific, consistent with the local surface chemistry of the facet under examination. The rank order of hydrophilicity of specific facet was in good agreement with concentration of hydroxyl groups determined from X-ray photoelectron spectroscopy. IGC-FC was applied to measure [gamma]d/SV profile, which were in good agreement with the [gamma]d/SV values measured from contact angle on the corresponding single crystals. This technique was shown to be able to distinguish surface energy heterogeneity, homogeneity as well as subtle changes in the [gamma]d/SV distributions, due to variations in the crystal habits. The wettability of the model compounds was ranked based on the contact angle polarity and IGC surface energy heterogeneity distributions, and the spreadability of binder solution was assessed based on the thermodynamic spreading coefficients. The increase in surface wettability led to the increase in granule mean size and granule strength. Formulations with similar wetting behaviour resulted in similar granule size, whilst those formulations with dissimilar surface wettability were found to exhibit substantially different granulation behaviour. In conclusion, the materials surface chemistry plays a crucial role in granulation processes. Its thorough characterisation and understanding may lead to more controllable product attributes and improved final performances.
Supervisor: Heng, Jerry ; Williams, Daryl Sponsor: AstraZeneca
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.513535  DOI: Not available
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