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http://hdl.handle.net/11375/22073
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DC Field | Value | Language |
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dc.contributor.advisor | Thompson, Michael | - |
dc.contributor.author | Liu, Yang | - |
dc.date.accessioned | 2017-10-04T19:59:57Z | - |
dc.date.available | 2017-10-04T19:59:57Z | - |
dc.date.issued | 2017-11 | - |
dc.identifier.uri | http://hdl.handle.net/11375/22073 | - |
dc.description.abstract | Twin screw granulation has gained wide interest by pharmaceutical manufacturing and the industry is still trying to expand its application. This thesis will further explore this technique and try to develop a new granulation strategy based on similar machinery setups. This thesis is firstly focused on twin screw wet granulation by investigating the function of conveying elements upstream and downstream of the kneading blocks and the wetting behavior of ingredients, with immediate released and controlled released formulations, separately. Granular properties were found to be sensitive to the pitch of downstream conveying elements where larger and irregular shaped particles were found when higher pitch was used. Although these findings are consistent with the theories of granule growth proposed by earlier studies, chunks were prone to be produced when complicated formulations including hydroxypropyl methylcellulose (HPMC) were used but can be surprisingly diminished by higher barrel temperature. This is believed to relate to the wetting behavior of ingredients. Higher temperature was found to reduce water absorption capacity, particularly for HPMC due to the gel layer formation, which is proposed as the dominant bridging mechanism for particle growth at lower temperature. This water uptake as a function of temperature enables process modification to ensure equivalent wetting behavior amongst ingredients for proper particle size control. Stimulated by the difficulties brought by the water addition as above and the needs from industry, a novel granulation strategy has been developed within a twin screw granulator by heat assistance which is significantly different from dry granulation in a roller compactor or conventional hot melt granulation. In twin screw dry granulation, particle combination is caused by the melting/softening of polymer binders which occurred exclusively in the kneading block driven by the heat generated from frictional, conductive and plastic dissipation. By limiting the heat exposure for formulations, this new method has advantages over hot melt granulation by protecting the ingredients from thermal degradation. For parameters, higher screw speed and lower feed rates enabled more of the feed particles to increase in temperature in the granulation zone and hence develop stronger and larger granules for a given screw pitch. Formulations including a polymer binder with lower molecular weight could be granulated at lower screw speed and binder content by comparing two grades of hydroxypropyl methylcellulose with different molecular weights, AFFINISOLTM HPMC HME 100LV and 4M. In addition, formulations with a higher binder content were likely to granulate under a broader range of operating conditions and ingredients with extremely low coefficients of friction could retard the particle agglomeration by greatly reducing frictional heat generation. | en_US |
dc.language.iso | en_US | en_US |
dc.title | TWIN SCREW WET AND DRY GRANULATION | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Chemical Engineering | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Doctor of Philosophy (PhD) | en_US |
dc.description.layabstract | Granulation is an important process to obtain a particular product known as “granules” which can be an intermediate between powder formulations and medical tablets in pharmaceutical industry. This thesis will further explore this granulation method by looking at screw configuration and the influence of heat from differing sources. Since screws can be configured with different components (screw elements), the study on functions of individual elements made up the first study in this thesis. The first section focused on twin-screw wet granulation where water is added during the process. The second body of work examined why particles were able to grow into granules by discussing the wetting ability of powders which affected by temperature. Because of disadvantages brought out by using water, a novel ‘twin-screw dry granulation’ technique was developed in this thesis using a similar screw configuration to twin-screw hot melt granulation. For this new technique, initial powder materials could be granulated directly without water addition. The last two sections in this thesis cover the new mechanism of granule growth by this technique, studying the influences of material and process parameters in order to provide guidance to the industry on its use and future research needed. | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Liu_Yang_201709_PhD.pdf | 6.06 MB | Adobe PDF | View/Open |
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