Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.665916
Title: Characterisation of tablets and roller-compacted ribbons with terahertz time-domain pulsed imaging
Author: Wall, Alexander
ISNI:       0000 0004 5351 9893
Awarding Body: De Montfort University
Current Institution: De Montfort University
Date of Award: 2015
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Abstract:
The pharmaceutical process of dry granulation using roller-compaction (DG/RC) is effectively a non-batch based procedure orientated to deliver a continuous stream of material free of a pre-defined batch-size with reduced plant equipment/scale-up R&D resources and an enhanced work-throughput, particularly suitable for moisture sensitive formulation. The desirable accreditations of DG/RC are many; yet by the nature of a more flexible approach than (i.e. wet-granulation), it must be highly monitored and controlled to accomplish higher-throughput rates and reduced ‘static’ material testing stages. To monitor rapidly and in-line with production, pre-granulated ribbons of RC (which highly correlates to the post milled granulates), terahertz time-domain spectroscopy (TDS) is used to elucidate the key physical attributes of post-compression density and thickness uniformity, key to end-product consistency. Invariably a great number of conditions apply to DG/RC (viz: System design, material characteristics, environmental and unit configuration), although widely regarded as the key processing parameters (PP’s) are roll-pressure and roll-gap [1-4]. The target of the study is to derive a strategy to position TDS as PAT to DG/RC. Two terahertz time-domain TD methods of a conventional transmission setup and reflection (TPI) THz analysis are used on standards of glass slides for verifying the interpretational foundations of the TD methods. Achieving RI/thickness error-discrepancies +2.2 to -0.4% c.f. literature ([150]) values provides foundations to test the solid-fraction ratios of pharma tablets with regard to RI’s being surrogate values to SF/path-length (R2 = 1). Combining transmission principles to the portion of reflected EMR removes the pre-requisite for RI or path-length knowledge, giving +1.5 to +2.4% RI agreement (vs. frequency-domain attained results) thus enabling thickness estimations to be above 95% against physical micrometre judgement in all models. Augmentation of the TD methods, refined in Experimental chapter 2 ,then chiefly focuses on TPI as the principle THz-TD method (as the most ideal tool for PAT) for adopting the RI measures for ribbon uniformity analysis in Experimental chapter 4 in an off-line environment again resulting in RI and thicknesses < 5 % error of known parameters of thickness and further use of RI as a proxy porosity equivalent to gas pycnometry. Elucidated in the work are the limitations encountered with tablets and RC’s, data interpretation of industrial considerations. Experimental chapter 3 diverges from RI to differentiate thickness in-order to assess the FD transmission for non-destructive mechanical assessment. This demonstrates a clear relationship between compaction force and the surrogate value for density, following a linear trend below a certain threshold of force. The ‘threshold’ value is observed for less massive tablets, and concluded is that the mechanistic interplay and permanent (plastic) consolidation is greater in instances where compaction-force increases proportionally with target-fill weights, and thus the various behaviour of MCC to stress.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.665916  DOI: Not available
Keywords: Terahertz Pulsed Imagaing ; Terahertz Time-Domain Imaging ; Characterisation of Roller-Compacts ; Terahertz Imaging of Roller-Compacts ; Terahertz Imaging of tablets ; THz-RC
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