dc.contributor.advisor |
Wu, Z |
en |
dc.contributor.advisor |
Alany, R |
en |
dc.contributor.author |
Hong, Lei |
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dc.date.accessioned |
2012-03-07T22:10:35Z |
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dc.date.issued |
2012 |
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dc.identifier.uri |
http://hdl.handle.net/2292/13343 |
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dc.description |
Full text is available to authenticated members of The University of Auckland only. |
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dc.description.abstract |
Background and Aim: Rumensin® Capsule has been marketed in the world for decades. However, it has been implemented that a benzene-free material must be used in product sold in Europe. As carbomer 934P in Rumensin® Capsule failed to meet this specification, therefore the aim of this thesis is to investigate an alternative carbomer, which can be equivalent to carbomer 934P in terms of product effectiveness and also complies with raw material speciation as required by EMEA. With the development of a new formulation, the optimisation of process parameters and establishment of in vitro and in vivo correlations (IVIVC) were also investigated. Methods: The Rumensin® Capsule was reformulated by fine-tuning of the different carbomers and their concentrations. The resultant tablets were assessed with respect to physiochemical properties, in vitro and in vivo release behaviors. The manufacture process for new formulation adopted that of Rumensin® Capsule, but it has been optimised by means of identifying the critical control variables that has a negative impact on the growth of the granules and the formation of the tablets. In the last section of this thesis, in vitro and in vivo data were compared and IVIVC models used to explain the correlations of these data were developed by means of mathematical linear regression models. Results and Discussion: A new formulation designed for European market has been successfully developed and has been demonstrated the equivalency to Rumensin® Capsule in terms of meeting the desirable specification using in vitro release studies, as well as in vivo studies in cattle. Instead of two-spray, a single-spray granulation process was developed to simplify the procedure. The tablets manufactured by revised process parameters in granulation and tablet compression together with the introduction of a new diffuser have been also evaluated and found to achieve the predetermined specification. A significant Level A linear correlation (R2 > 0.96) was found between in vitro tank release and in vivo release for individual formulation and a validated Level C model with correlation coefficient more than 0.92 was used to predict in vivo release rate. Conclusions: This thesis presented the development of a new formulation designed for European market and also the optimization of its manufacturing process. The results of tablets properties and release profiles showed that the developed product complied with European standard and was in parallel to Rumensin® Capsule, particularly both showed zero-order release thanks to the same capsule device used. The modification of drying process from two-spray to single-spray together with other process variables had an impact on drug release, but release rate can be easily controlled by use of different orifice diameters. This optimisation of process improved the production efficiency. The meaningful IVIVC model A and C have been established and indicated that the in vitro tank method for drug release was considered to be discriminative to determine the difference in formulation. Based on established IVIVC models, good prediction of in vivo product performance can be achieved. |
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dc.publisher |
ResearchSpace@Auckland |
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dc.relation.ispartof |
Masters Thesis - University of Auckland |
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dc.relation.replaces |
http://hdl.handle.net/2292/13335 |
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dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
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dc.title |
Development of a Veterinary Controlled-Release Intra-Ruminal Capsule and IVIVC Analysis |
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dc.type |
Thesis |
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thesis.degree.grantor |
The University of Auckland |
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thesis.degree.level |
Masters |
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dc.rights.holder |
Copyright: The author |
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pubs.elements-id |
314649 |
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pubs.record-created-at-source-date |
2012-03-08 |
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dc.identifier.wikidata |
Q112890001 |
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