Characterisation of Tablets and Roller-Compacted Ribbons with Terahertz Time-Domain Pulsed Imaging
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 () 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.
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Quantification of residual crystallinity in ball milled commercially sourced lactose monohydrate by thermo-analytical techniques and terahertz spectroscopy The quantification of crystallinity is necessary in order to be able to control the milling process. The use of thermal analysis for this assessment presents certain challenges, particularly in the case of crystal hydrates. ...