Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.702647
Title: Twin screw wet granulation of pharmaceutical powders : role of binder
Author: Saleh, Mohammed
ISNI:       0000 0004 6058 6031
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2016
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Abstract:
Several manufacturing industries are looking into transferring from batch operation to continuous operations, due to advantages offered in ease of scale up and high throughput. The Twin Screw Granulator (TSG) offers continuous manufacturing. However, there is still a knowledge gap in completely understanding the mechanisms of the continuous granulation. This includes understanding the effect of the critical parameters on the granulation process and the product properties. This will enable optimizing the operation condition to obtain the desired granule properties (i.e. desired granulation) while minimizing powder caking onto the barrel surface (i.e. undesired granulation). This research focuses on investigating the influence of the liquid binder viscosity at varying shear stresses, on both desired and undesired granulation. Different powders with different properties were considered to gain better appreciation of the importance of liquid-powder interaction. The research showed that both desired and undesired granulation was affected by the liquid binder viscosity. The effect of liquid binder viscosity varied as the shear stress applied was changed as well as the type of powder being used. During low shear stress (i.e. conveying element only), increasing liquid binder viscosity limited the spreading of the liquid. This limitation showed to give similar trends for the desired granulation regardless of the powder property, while the undesired granulation showed to be influenced by the powder property. For desired granulation, the granules size distribution widens with increasing the liquid viscosity, with elongated granules. The primary particles on the surface remained unaffected, while loosely bonded, creating considerable air voids within its internal structure. For undesired granulation, the way the powder caked to the surface of the barrel showed to be independent of the powder property, while showing difference when the liquid binder viscosity is changed. Using low liquid binder viscosity resulted in powder caking, initiating from the side and advancing to the centre, while the high liquid binder viscosity resulted in powder caking to be initiated from the centre of the barrel. On the other hand, the mass of powder caking onto the surface of the barrel was influenced by both the liquid binder viscosity and powder property. Increasing the liquid binder viscosity resulted in a reduction in the mass of powder caking for lactose and MCC. Whereas for the formulation, the amount of powder caking on the barrel surface, decreased first followed by a significant increase with increasing liquid binder viscosity. Increasing the shear stress applied on the material (i.e. using conveying and kneading elements) resulted in different trends in the properties of granules (desired granulation) and powder caking (undesired granulation) as the liquid binder viscosity increased, when compared with their corresponding trends whilst applying low shear stress. The increase in shear stress helped to improve the spreading and mixing of liquid binder with the powder (particularly for higher liquid binder viscosity). For desired granulation, the lactose powder showed growth, in particular for the viscous liquid binder, due to the enhanced mixing while a reduction in big granules (=3000 µm) for MCC and formulation. Also, the granules tended to have a rougher surface as the liquid binder viscosity was increased, regardless of the material. The granule's surface topography showed to be more compacted and with less air voids within its internal structure. This was more influenced by the increase in the stress rather than the liquid binder viscosity or material property. For undesired granulation, the powder caking showed to give uniform behaviour (i.e. propagating from the side of the barrel) regardless of the liquid binder viscosity or the powder property. On the other hand, the mass of powder caking showed to be dependent on the powder property and the liquid binder viscosity. The ribbon of caked powder showed to have more compacted surface topography with less air voids internally, regardless of powder property and liquid binder viscosity. The tendency of powder caking showed possible influences in the integrity of the product, different powders within a blend showed a difference in tendency to adhere to the surface of the barrel. Finally, the liquid binder viscosity and shear stress showed to influence the surface velocity of the granules which was measured using the PIV. The granules showed different surface velocity when moving from one screw to another, due to obstructions in the regions between the two screws. Generally, for low shear stress, depending on the liquid binder viscosity and the property of the material, obstruction between screws was more prominent to occur. Increasing the shear stress reduced the level of obstruction, while reducing the difference in momentum gained as well as a lower surface velocity of the granules in both screws.
Supervisor: Salman, Agba D. ; Hounslow, Michael J. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.702647  DOI: Not available
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