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Bodle Street, United Kingdom

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Bodle Street, United Kingdom
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Rough S.L.,New Museums Site | Wilson D.I.,New Museums Site
International Journal of Pharmaceutics | Year: 2010

The aim of the current work was to develop an extrusion-spheronisation (E-S) route to manufacture pellets with a high loading (≥90. wt%) of 5-aminosalicylic acid (5-ASA). Ram extrusion studies, supported by centrifuge testing, were employed to investigate the effect of the chemical (acidity) and physical (particle size and shape) characteristics of 5-ASA on the ability of microcrystalline cellulose (MCC)-based pastes to retain water when subjected to pressure. Liquid phase migration (LPM) within the paste during the extrusion, and hence variation in water content of extrudates and reproducibility of the final E-S product, was generally observed. The extent of LPM was found to be related to both the drug loading and its physical properties, most notably the particle shape (needle-like). A reduction in particle size, combined with a change in the shape of the 5-ASA particles, allowed LPM to be reduced considerably or eliminated. The performance of colloidal grades of MCC (Avicel RC591 and CL611) as alternative extrusion aids to the standard Avicel PH101 was also investigated: these proved to be superior aids for the highly loaded 5-ASA pastes as their greater water retention capacity mitigated LPM. Combining these results yielded a route for manufacturing pellets with 5-ASA loading ≥90. wt%. © 2010 Elsevier B.V.


Mascia S.,New Museums Site | Seiler C.,Merck And Co. | Fitzpatrick S.,Merck And Co. | Wilson D.I.,New Museums Site
International Journal of Pharmaceutics | Year: 2010

An experimental investigation of extrusion-spheronisation (E-S) of a novel microcrystalline cellulose (MCC) formulation, comprising dimethyl sulfoxide (DMSO) as the granulating liquid, is reported. The extrusion-spheronisation performance of DMSO/MCC pastes is compared to that of similar water/MCC formulations and their rheological behaviours similarly assessed using lubricated squeeze flow. A case study involving water, DMSO and anhydrous ethanol yields important information regarding the physico-chemical properties necessary for solvents to be suitable for the extrusion of MCC. © 2010 Elsevier B.V. All rights reserved.


Zhang M.,New Museums Site | Rough S.L.,New Museums Site | Ward R.,MSD | Seiler C.,MSD | Wilson D.I.,New Museums Site
International Journal of Pharmaceutics | Year: 2011

The use of multi-holed dies as an alternative to single-holed dies for generating extrudates for spheronisation was investigated both in terms of extrusion and spheronisation performance. A model 45 wt% microcrystalline cellulose (MCC)/water paste was employed in ram extrusion tests with square-ended dies with 1, 6, 33 and 137 holes, all of diameter 1 mm and length 2 mm. The extrudates generated using the multi-holed dies yielded pellets with comparable sphericity to those using the single-holed die. Multi-holed dies could also be operated with lower paste flow rates before encountering liquid phase migration (LPM). The characteristic processing velocity for the onset of LPM was determined for each die configuration and supported the hypothesis that LPM was caused by suction effects. A simple model of the flow pattern in a lab-scale Fuji-Paudal frontal screen extruder is presented which yields estimates of velocities and shear rates involved in these devices. The pressure required to extrude the paste through multi-holed dies was compared with the model proposed by Benbow and co-workers. The paste rheology was characterised using the Benbow-Bridgwater approach, employing 1, 2 and 3 mm diameter dies of various lengths. The Benbow et al. model under-predicted the observed extrusion pressure, which was attributed to its failure to account for the redundant work contribution in these complex flows. © 2011 Elsevier B.V. All rights reserved.


Wilson D.I.,New Museums Site | Rough S.L.,New Museums Site
European Journal of Pharmaceutical Sciences | Year: 2012

Pellets with high loading of 5-aminosalicylic acid (5-ASA, mesalamine) are desired to reduce the number of tablets required to deliver the daily dosing regimen. Recently, we reported an extrusion-spheronisation route for the development of a 90 wt% 5-ASA/microcrystalline cellulose formulation based on milled 5-ASA which gave good yields of pellets at the lab scale. In the present work, such formulation was optimised further by preliminary studies using a lab-scale ram extruder, and then scaled up to the pilot plant scale on a Nica screen extruder using a mixed fractional factorial approach. The final formulation featured 95 wt% 5-ASA and 5 wt% Avicel RC591 (all dry basis) and yielded spherical pellets suitable for use as the drug core of a multi-particulate DDS. © 2011 Elsevier B.V. All rights reserved.


Elvira K.S.,ETH Zurich | Wootton R.C.R.,ETH Zurich | Reis N.M.,Loughborough University | Mackley M.R.,New Museums Site | DeMello A.J.,ETH Zurich
ACS Sustainable Chemistry and Engineering | Year: 2013

Singlet oxygen, a reactive oxygen species, has been a basic synthetic tool in the laboratory for many years. It can be generated either through a chemical process or most commonly via a photochemical process mediated by a sensitizing dye. The relative paucity of singlet oxygen employment in fine chemical industrial settings can be attributed to many factors, not least the requirement for excessive quantities of oxygenated organic solvents and the dangers that these represent. Microcapillary films (MCFs) are comprised of multiple parallel channels embedded in a plastic film. In this study, MCFs are employed as flow reactor systems for the singlet oxygen mediated synthesis of ascaridole. No gaseous oxygen is supplied directly to the reaction, rather mass transport occurs exclusively through the reactor walls. The rate of production of ascaridole was found to be strongly dependent on the partial pressure of oxygen present within the reaction system. This methodology significantly simplifies reactor design, allows for increased safety of operation, and provides for space-time yields over 20 times larger than the corresponding bulk synthesis. © 2013 American Chemical Society.


Magens O.M.,New Museums Site | Ishiyama E.M.,IHS Downstream Research | Wilson D.I.,New Museums Site
Applied Thermal Engineering | Year: 2016

Fouling is a chronic problem in many heat transfer systems and leads to regular cleaning of heat exchangers. Antifouling coatings are one mitigation option: The financial attractiveness of installing a coated exchanger depends on trade-offs between capital and operating costs over the lifetime of the unit. Such considerations effectively set bounds on the price of coatings, bounded by manufacturing costs and the maximum saving that can be achieved from fouling mitigation, in a 'value pricing' calculation. The 'value pricing' concept is considered here, for the first time, for heat exchangers subject to asymptotic fouling. An explicit solution to the cleaning scheduling optimisation problem is presented for the case of equal heat capacity flow rates in a counter-current single phase exchanger. A case study is used to illustrate the concepts and key learnings. A sensitivity analysis identifies scenarios where the use of antifouling coatings may be attractive, and also where there is no financial benefit in cleaning a fouled exchanger. © 2016 Elsevier Ltd. All rights reserved.


Wilson D.I.,New Museums Site | Rough S.L.,New Museums Site
Canadian Journal of Chemical Engineering | Year: 2012

The multi-phase nature of granular pastes, coupled with their non-Newtonian rheology and inherent inhomogeneity, makes characterisation and prediction of flow behaviour challenging. We focus on 'stiff' pastes which can maintain their shape after extrusion. We describe how the approach presented by Benbow and Bridgwater can be used to predict the deformation and flow behaviour of such materials. Illustrations are drawn from industrial pastes and applications studied in our group. Its basis in viscoplasticity and pure plasticity is discussed. Problems associated with 'stiff' pastes are highlighted. Finally, a roadmap is presented summarising how we think the progress of paste understanding needs to be developed. © 2011 Canadian Society for Chemical Engineering.


Salley B.,New Museums Site | Gordon P.W.,New Museums Site | McCormick A.J.,New Museums Site | Fisher A.C.,New Museums Site | Wilson D.I.,New Museums Site
Biofouling | Year: 2012

A new configuration of the fluid dynamic gauging technique for measuring soft layers on surfaces was used to monitor the growth of a cyanobacterium, Synechococcus sp. WH 5701, on stainless steel (SS), glass and an indium tinoxide (ITO) on a polyethylene terephthalate (PET) substratum. The biofilm thickness increased steadily over 4weeks and exhibited noticeable changes in microstructure and strength. The biofilms all exhibited a two-layer structure, with a compact layer next to the substratum and a loose layer above. Biofilms on ITO or SS exhibited cohesive failure when removed by fluid shear whereas those on glass exhibited adhesive failure. The technique is able to elucidate various aspects of biofilm behaviour, as illustrated by the action of a biocide (NaOCl) on a mature biofilm. © 2012 Copyright Taylor and Francis Group, LLC.


Pogiatzis T.,New Museums Site | Ishiyama E.M.,New Museums Site | Paterson W.R.,New Museums Site | Vassiliadis V.S.,New Museums Site | Wilson D.I.,New Museums Site
Applied Energy | Year: 2012

Fouling of heat exchangers causes reduced heat transfer and other penalties. Regular cleaning represents one widely used fouling mitigation strategy, where the schedule of cleaning actions can be optimised to minimise the cost of fouling. This paper investigates, for the first time, the situation where there are two cleaning methods available so that the mode of cleaning has to be selected as well as the cleaning interval. Ageing is assumed to convert the initial deposit, labelled 'gel', into a harder and more conductive form, labelled 'coke', which cannot be removed by one of the cleaning methods. The second method can remove both the gel layer and the coke layer, but costs more and requires the unit to be off-line longer for cleaning. Experimental data demonstrating the effects of ageing are presented. The industrial application is the comparison of cleaning-in-place methods with off-line mechanical cleaning. A process model is constructed for an isolated counter-current heat exchanger subject to fouling, where ageing is described by a simple two-layer model. Solutions generated by an NLP-based approach prove to be superior to a simpler heuristic. A series of case studies demonstrate that combinations of chemical and mechanical cleaning can be superior to mechanical cleaning alone for certain combinations of parameters. © 2011 Elsevier Ltd.


Wang S.,New Museums Site | Wilson D.I.,New Museums Site
Industrial and Engineering Chemistry Research | Year: 2015

A benchtop fluid-dynamic gauging device to study the swelling or shrinking of soft solid layers immersed in a liquid environment in situ and in real time is demonstrated. A particular feature is that the volume of liquid is isolated, hence the name zero-net-discharge fluid-dynamic gauging (ZFDG), which renders ZFDG suitable for aseptic operation. For the 1.78 mm nozzle diameter used here, calibration tests gave a resolution of ±5 ∼m and an uncertainty of ±10 ∼m. Computational fluid dynamics simulations indicated that the shear stress imposed on a layer being gauged differed between the successive suction and ejection stages in ZFDG. The swelling of poly(vinyl acetate) (PVA) layers (about 1 mm dry thickness) and gelatin films (50-80 ∼m dry thickness) in aqueous solutions is reported as a demonstration of ZFDG application. There was good agreement with more cumbersome gravimetric methods. The gelatin swelled noticeably faster at high pH, above the pKa values of proline and hydroxyproline. Fitting the gelatin swelling data to a power law model indicated sub-Fickian behavior with a diffusion index that increased with the pH. © 2015 American Chemical Society.

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