Crystallisation is gaining a lot of interest in pharmaceutical industry to help designing active ingredients with tailored physicochemical properties. Many factors have been found to affect the crystallisation process, including process parameters and material attributes. Several studies in the literature have discussed the role of these parameters in the crystallisation process. A comprehensive study is still missing in this field where all the significant terms are taken into consideration, including the square effect and the interaction terms between different parameters. In this study, a thorough investigation into the main factors affecting crystallisation of a polymeric system, processed via injection moulding, was presented and a sample of response optimisation was introduced which can be mimicked to suite a specific need. Three grades of pure polyethylene oxide; 20K, 200K and 2M, were first characterised using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD) and shear rheometry. The onset of degradation and the rate varied according to molecular weight of polyethylene oxide (PEO). The peak melting temperature and the difference in enthalpy between melting and crystallisation were both in a direct proportion with PEO molecular weight. PEO200K and PEO2M struggle to recrystallise to the same extent of the original state at the tested cooling rates, while PEO20K can retain up to a similar crystallinity degree when cooled at 1 °C/min. Onset of crystallisation temperature (Tc1) was high for PEO2M and the difference between the 20K and 200K were pronounced at low cooling rate (20K is higher than 200K). The rheometer study showed that PEO2M has a solid-like structure around melting point which explains the difficulty in processing this grade at a low temperature via IM. PEO20K was almost stable within the strain values studied (Newtonian behaviour). For higher grades, PEO showed a shear thinning behaviour. The complex viscosity for PEO2M is characterised by a steeper slope compared to PEO200K, which indicates higher shear thinning sensitivity due to higher entanglement of the longer chains. For binary blends of PEO, the enthalpy of crystallisation studied by DSC was in direct proportion to the lowest molecular weight PEO content (PEOL %) in PEO20K/200K and PEO20K/2M blends. The effect of PEOL% on Tc1 became slightly pronounced for PEO20K-2M blends where Tc1 exhibited slight inverse proportionality to PEOL% and it became more significant for PEO200K-2M blends. It was interesting to find that Tc1 for the blends did not necessarily lie between the values of the homopolymers. In all binary blends, Tc1 was inversely proportional to cooling rate for the set of cooling rates tested. Thermal analysis using hot stage polarised light microscopy yields different behaviours of various PEO grades against the first detection of crystals especially where the lowest grade showed highest detection temperature. Visual observation of PEO binary blends caplets processed at various conditions via injection moulding (IM) showed the low-quality caplets processed at mould temperature above Tc1 of the sample. The factors affecting crystallisation of injection moulded caplets were studied using response surface methodology for two responses; peak melting temperature (Tm) and relative change in crystallinity (∆Xc%) compared to an unprocessed sample. Mould temperature (Tmould) was the most significant factor in all binary blend models. The relationship between Tmould and the two responses was positive non-linear at the Tmould ˂ Tc1. Injection speed was also a significant factor for both responses in PEO20K-200K blends. For Tm, the injection speed had a positive linear relationship while the opposite trend was found for ∆Xc%. The interaction term found in the RSM study for all models was only between the injection speed and the PEOL % which shows the couple effect between these two factors. Molecular effect was considered a significant factor in all ∆Xc% models across the three binary blends. The order of ∆Xc% sensitivity to the change in PEOL% was 3, 5 and 7 % for 20K-200K, 200K-2M and 20K-2M.

The feasibility of the injection moulding (IM) was explored for the development of novel drug delivery systems. Controlled release formulations were developed using a substituted cellulose derivative, hydroxypropyl methyl cellulose acetate succinate (HPMCAS) and a graft co-polymer (Soluplus®). BCS class II drugs ibuprofen and the felodipine were selected based on their physicochemical properties. In the present work, a homogenous dispersion of drugs in the polymer matrices was achieved using Hot Melt Extrusion (HME) and extruded pellets obtained were used for the development of the injection moulded systems. Four systems were developed using the IM consisting of ibuprofen-HPMCAS, ibuprofen-Soluplus®, felodipine-PEO-HPMCAS and felodipine-Soluplus®. The ibuprofen acts as a good plasticiser compared to felodipine therefore, felodipine containing IM systems required a plasticiser (PEO) when processed with HPMCAS. The analysis of extruded pellets and injection moulded systems using modulated DSC (MDSC) and Raman spectroscopy confirmed the formation of an amorphous molecular dispersion (i.e solid solution) in the case of all four systems. The phase separation behaviour and the amorphous stability of the systems was studied at various stress conditions. This revealed the “surface crystallisation” behaviour of the ibuprofen-HPMCAS systems. Temperature-composition phase diagram constructed based on the melting point depression and the Flory-Huggins lattice solution theory provided the explanation for the phase separation and crystallisation behaviour of ibuprofen-HPMCAS systems. The advanced characterisation techniques like DMA, 2D XRD and 3D laser microscopy provided the detailed understanding of crystal habits, phase seperation and surface crystallisation. The significant effect of the stress conditions on the rate of shrinkage was observed where, higher shrinkage tendency of a HPMCAS IM system was observed compared to Soluplus® IM systems. The extruded pellets provided the faster drug release compared to the moulded tablets suggests the effect of particle size as well as the densification during IM on the dissolution rate of the dosage form. The nature of the polymer and processing history were the contributing factors for the dissolution of the dosage forms. / The thesis is hardbound in two volumes. Volume II starts at Chapter 5, page 135.

The emergence of microneedle (MN) technologies offers a route for a pain free, straightforward and efficient way of transdermal drug delivery, but technological barriers still exist which pose significant challenges for manufacture of MN systems with high volume outputs at low cost. The main aim of this research was to develop new ways for MN manufacture primarily using micro-injection moulding processes with high performance engineering thermoplastics. During the moulding process these polymeric melts will be subjected to extreme stress and temperature gradients and detailed material characterisation combined with in-line monitoring is desirable to optimise the moulding parameters and will help in achieving sharp microneedles with acceptable quality. Hence high shear rheology of these selected materials was performed at wall shear rates carried out in excess of 107 s-1 over a range of temperatures to predict the flow behaviour of polymer melts at such high shear strain rates. This information was fed into injection moulding simulation software tools (Moldflow) to assist the MN production process design. The optimal design was then used to produce a full 3D solid model of the injection mould and mould insert. Furthermore various design of experiments were conducted considering input parameters such as injection pressure, injection speed, melt temperature, filling time and mould cavity temperature. Response variables including product quality and data acquired from the cavity pressure and temperature transducers were used to optimise the manufacturing process. The moulded MNs were geometrically assessed using a range of characterisation techniques such as atomic force microscopy, confocal microscopy and scanning electron microscopy. An attempt to make hollow MNs was performed and encountered many challenges like partial cavity filling and part ejection during processing. Studies were carried out to understand the problem and identified the major problem was in tool design and improvements to the moulding tool design were recommended. Plasma treatment and mechanical abrasion were employed to increase the surface energy of the moulded polymer surfaces with the aim of enhancing protein adsorption. Sample surface structures before and after treatment were studied using AFM and surface energies have been obtained using contact angle measurement and calculated using Owens-Wendt theory. Adsorption performance of bovine serum albumin and release kinetics for each sample set was assessed using a Franz diffusion cell. Results indicate that plasma treatment significantly increases the surface energy and roughness resulting in better adsorption and release of BSA. To assist design-optimisation and to assess performance, a greater understanding of MN penetration behaviour is required. Contact stiffness, failure strength and creep behaviour were measured during compression tests of MN against a steel surface, and in-vitro penetration of MNs into porcine skin. The MN penetration process into porcine skin was imaged using optical coherence tomography. Finally, a finite element model of skin was established to understand the effect of tip geometry on penetration. The output of findings from this research will provide proof of concept level development and understanding of mechanisms of MN penetration and failure, facilitating design improvements for micro-injection moulded polymeric MNs.

Yes / Plasma technology has been widely used to increase the surface energy of the polymer surfaces for many industrial applications; in particular to increase in wettability. The present work was carried out to investigate how surface modification using plasma treatment modifies the surface energy of micro-injection moulded microneedles and its influence on drug delivery. Microneedles of polyether ether ketone and polycarbonate and have been manufactured using micro-injection moulding and samples from each production batch have been subsequently subjected to a range of plasma treatment. These samples were coated with bovine serum albumin to study the protein adsorption on these treated polymer surfaces. Sample surfaces structures, before and after treatment, were studied using atomic force microscope and surface energies have been obtained using contact angle measurement and calculated using the Owens-Wendt theory. Adsorption performance of bovine serum albumin and release kinetics for each sample set was assessed using a Franz diffusion cell. Results indicate that plasma treatment significantly increases the surface energy and roughness of the microneedles resulting in better adsorption and release of BSA.

Yes / An idealised model of core-out in water assisted injection moulding (WAIM) is set up to isolate the effect of cooling by the water on the deposited layer thickness. Based on simulations, this is investigated for a specific case as a function of Pearson number and power law index. It is found that cooling significantly reduces the layer thickness to the extent that a change in the flow regime ahead of the bubble, from bypass to recirculating flow, is possible. For shear thinning melts with high temperature coefficient of viscosity, the simulations show very low layer thickness, which may indicate unfavourable conditions for WAIM. Although in the real moulding situation, other effects will be superimposed on those found here, the results provide new insights into the fundamentals of WAIM. Investigation of other effects characterised by Fourier and Reynolds numbers will be reported subsequently. Some early process measurement results from an experimental WAIM mould are presented. Reductions in residual wall thickness are observed as the water injection set pressure is increased and the duration of water bubble penetration through the melt is determined experimentally. The formation of voids within the residual wall is noted and observed to reduce in severity with increasing water injection pressure. The presence of such voids can be detected by the signature from an infrared temperatures sensor.

no / Real-time diagnostics of ceramic powder injection molding using a commercial micromolding machine was performed using ultrasound. Miniature ultrasonic sensors were integrated onto the mold insert. Melt front, solidification, temperature variation and part detachment of the feedstock inside the mold cavity were observed. It has been demonstrated that ultrasonic velocity in feedstock inside the mold cavity, the ultrasonic contact duration during which the part and mold are in contact, and holding pressure can be used to assist with optimization of injection and cooling parameters to minimize energy consumption and maximize process efficiency.Real-time diagnostics of ceramic powder injection molding using a commercial micromolding machine was performed using ultrasound. Miniature ultrasonic sensors were integrated onto the mold insert. Melt front, solidification, temperature variation and part detachment of the feedstock inside the mold cavity were observed. It has been demonstrated that ultrasonic velocity in feedstock inside the mold cavity, the ultrasonic contact duration during which the part and mold are in contact, and holding pressure can be used to assist with optimization of injection and cooling parameters to minimize energy consumption and maximize process efficiency.

Yes / Industry-standard quality management systems such as Six Sigma and emerging Industry 4.0 compliant production processes demonstrate the importance of in-line condition monitoring of manufacturing methods for achieving the highest levels of product quality. Measurement data collected as the process is running can inform the operator about unexpected changes in machine operation or raw materials that could negatively impact production; and offer an opportunity for a process control intervention to stabilise production. However, micro-manufacturing production lines can pose a challenging environment for deploying such systems, since processing events can occur extremely rapidly and in harsh environments. Moreover, the small scale of micro-nano featured components can make sensor installation even more problematic. Recently, ultrasonic micromoulding has drawn attention in niche markets due to its unique advantages for processing thermoplastics as a new micro-manufacturing technology. The process differs from conventional moulding significantly by eliminating the need for a plasticising screw and using direct application of ultrasonic energy to melt the polymer. This offers numerous benefits such as decrease in energy usage, moulding at lower pressures, easier cleaning, and reduced material residence times, the latter which could be beneficial for pharma-grade polymers or polymers with active ingredients. However, very little work has been reported attempting to monitor the process using in-line measurements. This work aims to evaluate the characteristics of the ultrasonic micromoulding process for microinjection moulding of a microneedle array using a range of sensor technologies including: data recorded by the machine controller; a high-speed thermal camera and a cavity pressure transducer. The data has captured the highly dynamic process environment with a high degree of accuracy. The relationship between the process data and dimensional quality of the ultrasonically micromoulded products has been quantified and subsequently implemented as a cost-effective in-line quality assurance method. / Horizon 2020, the EU Framework Programme for Research and Innovation (Project ID: 674801). This research has also received funding and support from two other Horizon 2020 projects: HIMALAIA (Grant agreement No. 766871) and Laser4Fun (GA no. 675063)

This research investigates formulation, compounding and thin-wall injection moulding of Polypropylene/clay nanocomposites (PPCNs) prepared using conventional melt-state processes. An independent study on single screw extrusion dynamics using Design of Experiments (DoE) was performed first. Then the optimum formulation of PPCNs and compounding conditions were determined using this strategy. The outcomes from the DoE study were then applied to produce PPCN compounds for the subsequent study of thin-wall injection moulding, for which a novel four-cavity injection moulding system was designed using CAD software and a new moulding tool was constructed based upon this design. Subsequently, the effects of moulding conditions, nanoclay concentration and wall thickness on the injection moulded PPCN parts were investigated. Moreover, simulation of the injection moulding process was carried out to compare the predicted performance with that obtained in practice by measurement of real-time data using an in-cavity pressure sensor. For the selected materials, the optimum formulation is 4 wt% organoclay (DK4), 4 wt% compatibiliser (Polybond 3200, PPgMA) and 1.5 wt% co-intercalant (erucamide), as the maximum interlayer spacing of clay can be achieved in the selected experimental range. Furthermore, DoE investigations determined that a screw speed of 159 rpm and a feed rate of 5.4 kg/h are the optimum compounding conditions for the twin screw extruder used to obtain the highest tensile modulus and yield strength from the PPCN compounds. The optimised formulation of PPCNs and compounding conditions were adopted to manufacture PPCN materials for the study of thin-wall injection moulding. In the selected processing window, tensile modulus and yield strength increase significantly with decreasing injection speed, due to shear-induced orientation effects, exemplified by a significantly increased frozen layer thickness observed by optical microscopy (OM) and Moldflow® simulation. Furthermore, the TEM images indicate a strong orientation of clay particles in the flow direction, so the PPCN test pieces cut parallel to the flow direction have 36.4% higher tensile modulus and 13.6 % higher yield strength than those cut perpendicular to the flow direction, demonstrating the effects of shear induced orientation on the tensile properties of thin-wall injection moulded PPCN parts. In comparison to injection speed, mould temperature has very limited effects in the selected range investigated (25-55 °C), in this study. The changes in moulding conditions show no distinctive effects on PP crystallinity and intercalation behaviour of clay. Impact toughness of thin wall injection moulded PPCN parts is not significantly affected by either the changes in moulding conditions or clay concentration (1-5 %). The SEM images show no clear difference between the fracture surfaces of PPCN samples with different clay concentrations. TEM and XRD results suggest that higher intercalation but lower exfoliation is achieved in PPCN parts with higher clay content. The composites in the thin sections (at the end of flow) have 34 % higher tensile modulus and 11 % higher yield strength than in the thicker sections, although the thin sections show reduced d001 values. This is attributed to the significantly enhanced shear-induced particle/molecular orientation and more highly oriented frozen layer, according to TEM, OM and process simulation results. In terms of the reduced d001 values in the thin sections, it is proposed that the extreme shear conditions in the thin sections stretch the PP chains in the clay galleries to a much higher level, compaction of clay stacks occurs as less interspacing is needed to accommodate the stretched chains, but rapid cooling allows no time for the chains to relax and expand the galleries back. Overall, data obtained from both actual moulding and simulation indicate that injection speed is of utmost importance to the thin-wall injection moulding process, development of microstructure, and thus the resulting properties of the moulded PPCN parts, in the selected experimental ranges of this research.

This thesis describes the optimization process for the pitchfork developed by the company Sverigegrepen. The work was done at the department of Applied Mechanics at Uppsala University. The project were handed by Ångström Materials Academy together with Sverigegrepen The work included a major prestudy of plastic construction, plastic materials, plastic injection and strength of materials. By applying the laws of beam theory, a mathematical expression could be provided, explaining the behaviour of the pitchforks teeth. By studying the pitchfork with tools such as 3D- CAD and FEA-simulations, an area where high concentrations of stress were found, an area known to have frequent issues with strength. From this data several concepts were created with an increased strength and a better distribution of stress. The plastic material was evaluated and tested to find the most valuable material characteristics. The provided information was used to isolate different functions in plastic materials, which is crucial for the pitchforks further functionality.

De senaste decennierna har visat på en stor ökning av den textila konsumtionen som följd av efterfrågan, samtidigt som den textila återvinningen idag är nästintill obefintlig. Detta leder till att mycket av det textila materialet deponeras istället för att återvinnas, vilket innebär ett stort slöseri av redan befintlig råvara som skulle kunna användas till att skapa nytt textilt material. Genom att undersöka olika återvinningsmetoder och -processer skulle denna råvara kunna användas på nytt. Examensarbetet är en del av forskningsprojektet ”Från spill till guld” som leds av forskningsinstitutet Swerea IVF. Forskningsprojektets utgångspunkt är att minimera produktionsspill och att höja dess värde inom bland annat textilindustrin. Examensarbetet syftar till att undersöka termomekanisk återvinning av plagg gjorda av polyamid 6.6 (PA6.6) och elastan, smältspinna filament samt formspruta provstavar från denna nya polymerblandning utan att separera fibrerna. Andra syftet är att även hitta en lösning för produkterna som undersöks i detta examensarbete kan återvinnas i sin helhet, så att ingen demontering av produkterna ska behövas. Fyra olika plagg undersöktes i examensarbetet bestående av materialblandningen PA6.6 och elastan. Analyser av de fyra olika plaggen genomfördes för att fastställa materialen. Hela plagg tillverkade i de olika materialen klipptes eller maldes ned och smältes sedan om genom kompoundering, därefter tillverkades granulat. Materialen testades i spinnbarhet genom smältspinningsförsök, sedan smältspanns eller formsprutades materialen. Resultaten från smältspinningsförsöken analyserades i ljusmikroskop för att avgöra om elastanen är termoplastiskt eller inte då detta är en avgörande faktor vid smältspinning. Olika tester gjordes på materialen för att undersöka deras eventuella kemiska nedbrytning som resultat av kompoundering. Resultatet visade att smältspinning och formsprutning inte är möjligt från denna polymerblandning. Ett antagande kan göras att återvinningen inte fungerade på grund av PA6.6:s höga smälttemperatur, då elastanen antagligen bryts ned vid denna höga temperatur, vilket förstör materialet. Slutsatsen blir då att smältspinning och formsprutning inte är möjligt utifrån denna polymerblandning, men återvinning till plastdetaljer kan produceras vid kompounderingsstadiet och återanvändas i annan industri än textilindustrin. Potential finns för återvinning av plagg till plagg om ändringar görs under processens gång och om elastanen identifieras som termoplastisk eller inte. / The latest decades have shown a large increase in textile consumption as a result of demand, at the same time the textile recycling today is almost non-existent. This means that much of the textiles are used for landfill rather than being recycled, which generates a large waste of raw material that could be used to create new textiles. By exploring various recycling methods and processes this raw material could be used again. This thesis is part of a research project, “From Waste To Gold”, which is led by the research institute Swerea IVF. The research projects foundation is to minimize production waste and to increase its value in areas such as textile industries. This thesis’ foundation is to examine the mechanical recycling of garments made by polyamide 6.6 (PA6.6) and spandex, melt spin filaments and produce injection moulded samples from this new polymer blend, without separating the fibres. The other foundation is to find a solution for the products that are examined in this thesis so they could be recycled as a unit, no disassembly of the products would be necessary Four different garments was examined in this thesis, the materials were a combination of PA6.6 and spandex. Different analyses were made on the four different garments. Whole garments from the different materials were cut or milled and then re melted through compounding, after compounding granulates was made. The materials spin ability was tested through melt spinning trials, then the materials were either melt spun or injection moulded. The results from the spinning trials was analysed in a light microscope to examine if the spandex were thermoplastic or not, as this is a crucial factor when melt spinning. Various tests were conducted to analyse their chemical degradation after the compounding. The results from the melt spinning and injection moulding showed that it was not possible to recycle this polymer combination this way. An assumption can be made that the recycling methods did not work because of the high melt temperature of PA6.6, the spandex assumes to decompose at this high temperature and therefore destroys the material. The conclusion is that melt spinning and injection moulding is not possible to conduct with this polymer combination, but recycling to plastic details could be done at the compound stage and then be used in some other industry, not in the textile industry. There are potential for garment-to-garment recycling if changes are made during the recycling processes and if the spandex could be identified as a thermoplastic or a non-thermoplastic.