Canada is a major global producer of pulse products including pulse starch, which notably contributes to a healthy diet. Strategically, Canada is taking steps to research methods of adding greater value to these crop products, and functional foods like resistant starch are particularly interesting. The primary objectives of this study were to develop an effective reactive extrusion process to produce gelatinized lipid complexed pea starches with enhanced enzyme resistance and examine the effects of bulk lipid complexing conditions on physicochemical and functional properties of extruded pea starches. One type of commercially available pea starch, Nutri-Pea, was chosen as the research subject in this study. A number of methods including; Englyst digestion method, differential scanning calorimetry (DSC), infrared spectroscopy (FTIR), contact angle, titrations, residence time distribution (RTD) and rapid visco analysis (RVA) were used to characterize the properties of extruded pea starches. The effects of feed formulation and extrusion conditions on lipid complexing and Englyst digestion profiles were systematically examined on two mixing devices. An extensive kinetics study was conducted on a lab scale twin-screw compounder, DSM-Xplore. The process was then scaled up to produce bulk lipid complexed pea starch on a Leistritz twin-screw extruder. The results showed that lipid complexing and digestion profiles were highly dependent on feed moisture and induced screw shear. Reactive extrusion of pea starches under optimized conditions achieved a significant but moderate increase in either resistant starch (RS) content (from 13.3% to 20.2%) or slowly digestible starch (SDS) content (from 7.85% to 23.3%) compared to their native counterparts. However, RS and SDS content could not be improved simultaneously based on the pea starch and extrusion process in this study. Increased degree of substitution (DS) was found for myristic acid complexed pea starches (nominal DS= ~0.8) when compared to palmitic acid complexed pea starch (nominal DS= ~0.5). Contact angle measurements, FTIR and DSC thermograms confirmed the presence of lipids. Lipid complexed starch films showed increasing hydrophobicity with increasing lipid content. As an alternative product compared to functional foods, the modified starch was considered as a biodegradable film for industrial applications. The material was produced at the highest moisture content for extruded native starch and two concentrations of lipid complexed starch using an intensive screw design. Preliminary results show that increasing lipid content and adding 1% glycerol to samples decreases the force per film thickness required to puncture films. However further investigation is required to determine effect of heat and moisture deformation. / Thesis / Master of Applied Science (MASc) / Incorporation of pulses into food products has been a major area of Canadian research for its potential to create new avenues of enzyme resistant food starches. Extrusion cooking is commonly used in industry for producing various food products such as snacks and cereals but little research has been reported on using an extruder to rapidly produce resistant pulse starches as a functional ingredient on a large scale; resistant starch is a functional food beneficial to humans in the same manner as insoluble fiber but exhibits improved textural properties. This study aimed to develop an effective reactive extrusion process to produce lipid complexed pea starches with enhanced enzyme resistance (i.e. increased slowly digestible starch (SDS) and resistant starch (RS) content) by an examination of the effects of reaction conditions on the properties of extrusion products. The lipid complexed pea starches under optimized conditions achieved a significant but moderate increase in either RS content or SDS content depending on the sample formulation compared to their native counterparts. However, RS and SDS content could not simultaneously be improved in this study.

Twin screw wet granulation (TSG) has been studied as a continuous manufacturing alternative to batch granulation for nearly twenty years. One of the main differences between batch granulation and TSG lies in the exiting granules being presented as a bimodal particle size distribution (PSD) in the latter case. Current process analytical technologies (PAT) can monitor a monomodal distribution well but there have been no techniques disclosed in the public domain so far that can accurately monitor this unusually shaped PSD. Acoustic emissions (AE) has been identified as a PAT of interest due to its ease of use (lack of calibration), low cost, and non-invasive design relative to other PATs used for monitoring PSDs. Hence the goal of this thesis was to develop AE as a process analytical technology (PAT) capable of estimating the full distribution of produced granules by TSG in real time. The first research study of this thesis focused on the development of the new technology. The AE PAT consisted of an acoustic sensor, an impact plate, and software to convert the time-domain signal of particle collisions into a time-averaged frequency-domain spectrum to be subsequently used to estimate a weight-averaged particle size distribution. A novel and much required addition to the PAT was inclusion of a digital filter based on particle mechanics parameters to overcome auditory masking which hindered accurately converting the cumulative sounds of impact into a PSD. The PAT was tested in this study with granulated lactose monohydrate and with the new digital filter, obtaining a maximum error of 1 wt% across all particle sizes tested. In the second research study, as more formulations commonly used in the industry were tested, the filter proved unable by itself to account for the differences in impact mechanics and therefore needed to be modified to incorporate the more inelastic behaviour now being seen. Two micromechanical models were explored, and the Walton-and-Braun model was found to be the most suitable for the AE PAT – reducing its error from 8 wt% down to 2.75 wt% across four formulations producing coefficients of restitution from 0.79 to 0.24. In the last research study in this thesis, the now-functional inline PAT was used to reveal mechanistic details related to the transition state in granulation as a TSG starts up, to improve the field’s understanding of the granulation mechanism. The technique was able to estimate the PSD over much shorter periods of material collection compared to sieving, allowing the evolution of the PSD as a function of time to be examined for varying degrees of fill (DF) and liquid-to-solids ratios. It was determined that the time to steady state, at both DF tested, occurred at approximately 5 times the mean residence time of the process by both PAT and sieving analyses. Particle sizes between 102-2230 μm were then tracked as a function of time below 120 s and variations of granule growth were seen for each degree of fill which added to the understanding of the granulation mechanism. This PAT shows great promise as a monitoring tool to implement quality by design principles for TSG in pharmaceutical manufacturing. / Thesis / Doctor of Philosophy (PhD)

Yes / The effect of screw configuration on granule size distribution (GSD) using gPROMS FormulatedProduct (gFP) software to perform optimization, estimation of complex processes, and analyses is evaluated. Twin-screw granulation modeling was used to investigate the contribution of screw configuration and liquid-to-solid (L/S) ratio on GSD. Lactose and Avicel were the granulating materials. Twelve different configurations were investigated under three feed rates as consistent with literature and at various L/S ratios. Results indicate that kneading elements promote the recovery of 100–1000 µm granules while reducing the production of oversized granules. Higher feed rates support the production of fines and agglomerates, while a low feed rate produces 100–1000 µm granules. / Ghana Scholarship Secretariat

Yes / Twin-screw granulation has emerged as a key process in powder processing industries and in the pharmaceutical sector to produce granules with controlled properties. This comprehensive review provides an overview of the simulation techniques and approaches that have been employed in the study of twin-screw granulation processes. This review discusses the major aspects of the twin-screw granulation process which include the fundamental principles of twin-screw granulation, equipment design, process parameters, and simulation methodologies. It highlights the importance of operating conditions and formulation designs in powder flow dynamics, mixing behaviour, and particle interactions within the twin-screw granulator for enhancing product quality and process efficiency. Simulation techniques such as the population balance model (PBM), computational fluid dynamics (CFD), the discrete element method (DEM), process modelling software (PMS), and other coupled techniques are critically discussed with a focus on simulating twin-screw granulation processes. This paper examines the challenges and limitations associated with each simulation approach and provides insights into future research directions. Overall, this article serves as a valuable resource for researchers who intend to develop their understanding of twin-screw granulation and provides insights into the various techniques and approaches available for simulating the twin-screw granulation process.

Yes / A study on the translation of a solid-state synthetic reaction from a mechanochemical mixer-mill to a continuous twin-screw extruder is discussed herein. The study highlights some considerations to be made and parameters to be tested in the context of a model fluorination reaction, which is the first organic fluorination to be attempted using extrusion. Upon optimization, which features the first use of grinding auxiliary solids to enable effective synthetic extrusion, the difluorination reaction was successfully translated to the extruder, leading to a 100-fold improvement in Space Time Yield (STY); 29 kg m−3 day−1 in a mixer mill to 3395 kg m−3 day−1 in a twin screw extruder. / D. L. B is grateful to the EPSRC for a First Grant (D. L. B. EP/P002951/1), CRD for a studentship award to J. L. H., Queen’s University Belfast for a Visiting Research Fellowship and the School of Chemistry at Cardiff University for generous support. S. L. J. is grateful to EPSRC for support (EP/L019655/1).

No / Mechanochemical synthesis has been applied to the rapid synthesis of Deep Eutectic Solvents (DESs), including Reline 200 (choline chloride : urea, 1 : 2), in a continuous flow methodology by Twin Screw Extrusion (TSE). This gave products in higher purity and with Space Time Yields (STYs), four orders of magnitude greater than for batch methods

No / The oligomerisation of L-amino acids by papain was studied in a mixer ball mill and in a planetary ball mill. The biocatalyst proved stable under the ball milling conditions providing the corresponding oligopeptides in good to excellent yields and with a variable degree of polymerisation. Both parameters were found to be dependent on the reaction conditions and on the nature of the amino acid (specifically on its side-chain size and hydrophobicity). In addition, the chemoenzymatic oligomerisation was demonstrated by utilising twin-screw extrusion technology, which allowed for a scalable continuous process. Finally, the synthesised oligo(L-Leu) 2b proved to be active as a catalyst in the Juliá–Colonna enantioselective epoxidation of chalcone derivatives. / We acknowledge RWTH Aachen University for support by the Distinguished Professorship Program funded by the Excellence Initiative of the German federal and state governments. We kindly acknowledge Marcus Frings and Plamena Staleva for the HPLC analysis of products 4a–c (RWTH Aachen University) and ASEP for the TGA analysis (Queen’s University Belfast). D. E. C. and S. L. J. acknowledge the agency EPSRC, grant no. EP/R019655/1. Part of this work was performed at the Center for Chemical Polymer Technology (CPT) unit of DWI, which was supported by the EU and the federal state of North Rhine-Westphalia (grant EFRE 30 00 883 02).

Yes / The continuous and scalable synthesis of a porous organic cage (CC3), obtained through a 10-component imine polycondensation between triformylbenzene and a vicinal diamine, was achieved using twin screw extrusion (TSE). Compared to both batch and flow syntheses, the use of TSE enabled the large scale synthesis of CC3 using minimal solvent and in short reaction times, with liquid-assisted grinding (LAG) also promoting window-to-window crystal packing to form a 3-D diamondoid pore network in the solid state. A new kinetically trapped [3+5] product was also observed alongside the formation of the targeted [4+6] cage species. Post-synthetic purification by Soxhlet extraction of the as-extruded ‘technical grade’ mixture of CC3 and [3+5] species rendered the material porous. / Engineering and Physical Sciences Research Council (EPSRC) under the Grants EP/R005710/1 (AIC) and EP/R005540/1 (SLJ), and for an EPSRC Summer Vacation Bursary at the University of Liverpool (FG, RLG). We also thank the European Research Council under FP7, RobOT, ERC Grant Agreement No. 321156 (AIC), for financial support. RLG thanks the Royal Society for a University Research Fellowship.

Yes / Grinding solid reagents under solvent-free or low-solvent conditions (mechanochemistry) is emerging as a general synthetic technique which is an alternative to conventional solvent-intensive methods. However, it is essential to find ways to scale-up this type of synthesis if its promise of cleaner manufacturing is to be realised. Here, we demonstrate the use of twin screw and single screw extruders for the continuous synthesis of various metal complexes, including Ni(salen), Ni(NCS)2(PPh3)2 as well as the commercially important metal organic frameworks (MOFs) Cu3(BTC)2 (HKUST-1), Zn(2-methylimidazolate)2 (ZIF-8, MAF-4) and Al(fumarate)(OH). Notably, Al(fumarate)(OH) has not previously been synthesised mechanochemically. Quantitative conversions occur to give products at kg h−1 rates which, after activation, exhibit surface areas and pore volumes equivalent to those of materials produced by conventional solvent-based methods. Some reactions can be performed either under completely solvent-free conditions whereas others require the addition of small amounts of solvent (typically 3–4 mol equivalents). Continuous neat melt phase synthesis is also successfully demonstrated by both twin screw and single screw extrusion for ZIF-8. The latter technique provided ZIF-8 at 4 kg h−1. The space time yields (STYs) for these methods of up to 144 × 103 kg per m3 per day are orders of magnitude greater than STYs for other methods of making MOFs. Extrusion methods clearly enable scaling of mechanochemical and melt phase synthesis under solvent-free or low-solvent conditions, and may also be applied in synthesis more generally. / EPSRC (EP/L019655/1)

Yes / Chemical manufacturing typically requires more than one step, involving multiple batch processes, which makes synthesis at scale laborious and wasteful. Herein, we demonstrate that several reactions can be telescoped into a single continuous process and/or be carried out as a continuous multi-component reaction (MCR), by twin screw extrusion (TSE), in the complete absence of solvent. / EPSRC (EP/L019655/1).