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Title: Granule dissolution and disintegration
Author: Chen, Y.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2005
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Abstract:
The increasing use of granular materials in the chemical, petrochemical, food and pharmaceutical industries, both as intermediate and as end products, gives rise to the need for a better understanding of granule dissolution and disintegration (GDD). However, little is understood about the physical principles controlling the release of active ingredients from granules, a crucial knowledge for the design of product structure in order to optimise product performance. The aim of this work is to bring a scientific approach to the study of GDD in a systematic way. which has not been addressed hitherto. The work here is to highlight the testing of these hypotheses and provide insight into GDD mechanisms. The scientific concern in this thesis is to attempt to reveal the unique behaviour of GDD that is different from homogeneous material dissolution. Unlike homogeneous material dissolution, which depends mainly on the chemical properties of the solute and solvent, GDD is more complicated because the heterogeneous system involves mixed insoluble particles and soluble binder. Further complexity lies in the fact that various physical properties such as granule size, primary particle size, binder-solid ratio and internal pore structure play in influencing GDD behaviour. This thesis reports experiments and theoretical analysis of such GDD behaviour. Four hypotheses - reaction-limited consumption of binder, transport limit for binder removal, transport limit for particle removal and additional Hmit for particle and binder removal - were proposed to cover all of the possible GDD mechanisms. Theories were developed and experiments were set up to test the theory and give explanation of various limiting cases of GDD. A bimodal population balance model was developed. Furthermore, a dynamic shrinking-shell and core model was proposed to clarify GDD mechanisms. The analysis, which has its origin in comparing binder and particle transport coefficients, enables prediction of whether particle or binder transport will hmit GDD process. This evolved into a Sherwood number analysis, which provides a direct physical account of the controlling step. Based on a non-synchronous binder and particle transport analysis, a shrinking shell and core model was proposed to highlight that binder transport may be limited by internal particle shell build-up in the granule. A dynamic model was then developed to provide quantitative analysis of the binder Sherwood number, which was tested by experiment. A rigorous deduction of the model provided a clear physical meaning of the parameters in the equations. To demonstrate the theory and test hypotheses, an ionic binder, zeolite-NaLAS was used in high shear granulation, low shear granulation, fluidised bed granulation and spray drying granulation to provide a range of granule structures and to allow investigation of GDD by both PSD and electrical conductivity. Granules were characterised using mercury porosimetry, sieving, bulk density, particle size analyser and SEM to provide information concerning their various properties, such as binder content, internal pore structure and volume fraction, granule size and primary particle size distribution, as well as surface morphology and granule internal structure. Two main methodologies were adopted to investigate GDD behaviour including a): monitoring electrical conductivity and granule diameter simultaneously for a single granule; b) monitoring the evolution of the PSD by laser light scattering. Those results were analysed to support the theory. In general, the phenomena in GDD are quite different from the general cases of dissolution.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.597529  DOI: Not available
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