Incorporation and release of macromolecules from biodegradable polymer vehicles

The initial objective of this work was to evaluate and introduce fabrication techniques based on W/0/W double emulsion and 0/W single emulsion systems with solvent evaporation for the incorporation of a surrogate macromolecule (BSA) into microspheres and microcapsules fabricated using P(HB-HV}, PEA and their blends. Biodegradation, expressed as changes in the gross and ultrastructural morphology of BSA loaded microparticulates with time was monitored using SEM concomitant with BSA release. Spherical microparticulates were successfully fabricated using both the W/0/W and 0/W emulsion systems. Both microspheres and microcapsules released BSA over a period of 24 to 26 days. BSA release from P(HB-HV)20% PCL 11 microcapsules increased steadily with time, while BSA release from all other microparticulates was characterised by an initial lag phase followed by exponential release lasting 6-11 days. Microcapsules were found to biodegrade more rapidly than microspheres fabricated from the same polymer. The incubation of microparticulates in newborn calf serum; synthetic gastric juice and pancreatin solution showed that microspheres and microcapsules were susceptible to enzymatic biodegradation. The in vitro incubation of microparticulates in Hank's buffer demonstrated limited biodegradation of microspheres and microcapsules by simple chemical hydrolysis. BSA release was thought to ocurr as a result of the macromolecule diffusing through either inherent micropores or via pores and channels generated in situ by previously dissolved BSA. However, in all cases, irrespective of percentage loading or fabrication polymer, low encapsulation efficiencies were obtained with W/0/W and 0/W techniques (4.2±0.9%- 15.5±0.5%,n=3), thus restricting the use of these techniques for the generation of microparticulate sustained drug delivery devices. In order to overcome this low encapsulation efficiency, a W/0 single emulsion technique was developed and evaluated in an attempt to minimise the loss of the macromolecule into the continuous aqueous phase and increase encapsulation efficiency. Poly(lactide-co-glycolide) [PLCG] 75:25 and 50:50, PEA alone and PEA blended with PLCG 50:50 to accelerate biodegradation, were used to microencapsulate the water soluble antibiotic vancomycin, a putative replacement for gentamicin in the control of bacterial infection in orthopaedic surgery especially during total hip replacement. Spherical microspheres (17.39±6.89~m,n=74-56.5±13.8~m,n=70) were successfully fabricated with vancomycin loadings of 10, 25 and 50%, regardless of the polymer blend used. All microspheres remained structurally intact over the period of vancomycin release and exhibited high percentage yields( 40. 75±2 .86%- 97.16±4.3%,n=3)and encapsulation efficiencies (47.75±9.0%- 96.74±13.2%,n=12). PLCG 75:25 microspheres with a vancomycin loading of 50% were judged to be the most useful since they had an encapsulation efficiency of 96.74+13.2%, n=12 and sustained therapeutically significant vancomycin release (15-25μg/ml) for up to 26 days. This work has provided the means for the fabrication of a spectrum of prototype biodegradable microparticulates, whose biodegradation has been characterised in physiological media and which have the potential for the sustained delivery of therapeutically useful macromolecules including water soluble antibiotics for orthopaedic applications.

The fatigue ageing of vulcanised rubbers

The cause of the respective rough and smooth fatigue failure surfaces of Neoprene GS : Neoprene W and Neoprene GS : natural rubber vulcanisates is investigated. The contrasting morphology of the vulcanisates is found to be the major factor determining the fatigue behaviour of the blends. Neoprene GS and Neoprene W appear to form homogeneous blends which exhibit physical properties and fatigue failure surfaces intermediate between those of the two horropolymers. Neoprene GS and natural rubber exhibit heterogeneity when blended together. The morphology of these blends is found to influence both the fatigue resistance and failure surface of the vulcanisates. Exceptional uncut and cut initiated fatigue lives are observed for blends having an interconnecting network morphology. The network structure and cross-link density of the elastomers in the blends and the addition of carbon black and antioxidant are all found to influence the fatigue resistance but not the failure mechanism of the vulcanisate.

The behaviour of antioxidants in polyolefins under conditions of U.V. exposure

The effects of antioxidants and stabilizers on the oxidative degradation of polyolefins (low density polyethylene [LDPE] and polypropylene [PPJ have been studied after subjecting to prior high temperature processing treatments. The changes in the both chemical and physical properties of unstabilized polymers occurring during processing were found to be strongly dependent on the amount of oxygen present in the mixer. Subsequent thermal and photo-oxidation showed very similar characteristics and the chromophore primarily responsible for:both thermo and photooxidative degradation of unstabilized polymers was found to be hydroperoxide formed during processing. Removal of hydroperoxide by heat treatment in an inert atmosphere although increasing ketonic carbonyl concentration, markedly decreased the rate of photo-oxidation, introducing an induction period similar to that of an unprocessed sample. It was concluded that hydroperoxides are the most important initiators in normally processed polymers during the early stages of photo-oxidation. Antioxidants such as metal dithiocarbamates which act by destroying peroxides into non-radica1 products were found to be efficient melt stabilizers for polyolefins and effective UV stabilizers during the initial photo-oxidation stage, whilst a phenolic antioxidant, n-octadecyl-3-(3',5'-di-terbutyl 4'hydroxypheny1) propionate (Irganox 1076) retarded photo-oxidation rate in the later stages. A typical 'UV absorber' 2-hydroxy-4-octyloxy-benzophenone (HOBP) has a minor thermal antioxidant action but retarded photo-oxidation at all stages. A substituated piperidine derivative, Bis [2.2.6.6-tetramethylpiperidlnyl-4] sebacate (Tinuvin 770) behaved as an pro-oxidant during thermal oxidation of polyolefins but was an effective stabilizer against UV light. The UV absorber, HOBP synergised effectively with both peroxide decomposing antioxidants (metal dithiocarbamates) and a chain-breaking antioxidant (Irganox 1076) during photo-oxidation of the poymers studed whereas the combined effect was additive during thermal oxidation. By contrast, the peroxide decornposers and chain-breaking antioxidant (Irganox 1076) which were effective synergists during thermal oxidation of LDPE· were antagonistic during photo-oxidation. The mechanisms of these processes are discussed.

A techno-economic study of the recycling of mixed plastics to useful products

The techno-economic implications of recycling the components of mixed plastics waste have been studied in a two-part investigation: (a) An economic survey of the prospects for plastics recycling, the plastics waste arisings from retailing, building, automotive, light engineering and chemical industries have been surveyed by mans of questionnaires and interviews. This was partially successful and indicated that very considerable quantities of relatively clean plastics packaging was available in major department chains and household stores. The possibility of devising collection systems for such sources, which do not lead to any extra cost, have been suggested. However, the household collection of plastics waste has been found to be uneconomic due to high cost of collection, transportation and lack of markets for the end products. (b) In a technical study of blends of PE/PP and PE/PS which are found in admixture in waste plastics, it has been shown that they exhibit poor mechanical properties due to incompatibility. Consequently reprocessing of such unsegregated blends results in products of little technological value. The inclusion of some commercial block and graft copolymers which behave as solid phase dispersants (SPES) increase the toughness of the blends (e.g. EPDM in PE/PP blend and SBS in PE/PS blend). Also, EPDM is found to be very effective for improving the toughness of single component polypropylene. However, the improved Technical properties of such blends have been accompanied by a fast rate of photo-oxidation and loss of toughness due to the presence of unsaturation in SPD's. The change in mechanical properties occurring during oven ageing and ultra-violet light accelerated weathering of these binary and ternary blends was followed by a viscoelastonetric technique (Rheovibron) over 9,, wide range of temperatures, impact resistance at room temperature (20-41'G) and changes in functional groups (i.e. carbonyl and trans-1,4-polybutadiene). Also the heat and light stability of single and mixed plastics to which thiol antioxidants were bound to SPE1 segment have been studied and compared with conventional antioxidants. The long-term performance of the mixed plastics containing SPE1 have been improved significantly by the use of conventional and bound antioxidants. It is concluded that an estimated amount of 30000 tonnes/year of plastics waste is available from department chains and household stores which can be converted to useful end products. This justifies pilot-experiments in collaboration with supermarkets, recyclers and converters by use of low cost SPD's and additives designed to make the materials more compatible.

Alginates as therapeutic and drug delivery systems

Alginate is widely used as a viscosity enhancer in many different pharmaceutical formulations. The aim of this thesis is to quantitatively describe the functions of this polyelectrolyte in pharmaceutical systems. To do this the techniques used were Viscometry, Light Scattering, Continuous and Oscillatory Shear Rheometry, Numerical Analysis and Diffusion. Molecular characterization of the Alginate was carried out using Viscometry and Light Scattering to determine the molecular weight, the radius of gyration, the second virial coefficient and the Kuhn statistical segment length. The results showed good agreement with similar parameters obtained in previous studies. By blending Alginate with other polyelectrolytes, Xanthan Gum and 'Carbopol', in various proportions and with various methods of low and high shear preparation, a very wide range of dynamic rheological properties was found. Using oscillatory testing, the parameters often varied over several decades of magnitude. It was shown that the determination of the viscous and elastic components is particularly useful in describing the rheological 'profiles' of suspending agent blends and provides a step towards the non-empirical formulation of pharmaceutical disperse systems. Using numerical analysis of equations describing planar diffusion, it was shown that the analysis of drug release profiles alone does not provide unambiguous information about the mechanism of rate control. These principles were applied to the diffusion of Ibuprofen in Calcium Alginate gels. For diffusion in such non-Newtonian systems, emphasis was placed on the use of the elastic as well as the viscous component of viscoelasticity. It was found that the diffusion coefficients were relatively unaffected by increases in polymer concentration up to 5 per cent, yet the elasticities measured by oscillatory shear rheometry were increased. This was interpreted in the light of several theories of diffusion in gels.

Chloride resistance and durability of cement paste and concrete containing metakaolin

Metakaolin (MK), a calcined clay, was included as a partial cement replacement material, at up to 20% by weight of binder, in cement pastes and concrete, and its influence on the resistance to chloride ingress investigated. Reductions in effective chloride diffusion coefficients through hardened cement paste were obtained for binary blends and by combining OPC, MK and a second cement replacement material of pulverised fuel ash or ground granulated blast furnace slag. Steady state oxygen diffusion measurements through hardened cement pastes measured using an electrochemical cell showed that the interaction between charged species and the pore surfaces is a major factor in determining chloride diffusion rate. Rheology of the binder, particularly at high MK replacement levels, was found to have a dramatic influence on the diffusion performance of cement pastes. It was concluded that plasticising admixtures are essential for adequate dispersion of MK in cement pastes. Chloride concentration profile analysis of the concrete cylinders, exposed to sodium chloride solution for one year, was employed to obtain apparent chloride diffusion coefficients for concrete specimens. MK was found to reduce the depth of chloride penetration into concrete when compared with that of unblended mixes. Corrosion rate and corrosion potential measurements were taken on steel bars embedded in concrete exposed to a saline environment under conditions of cyclic wetting and drying. The initiation time for corrosion was found to be significantly longer for MK blended mixes than for plain OPC systems. The aggregate-paste interfacial zone of MK blended systems was investigated by steady state diffusion of chloride ions through mortar containing glass beads as model aggregate. For the model aggregate specimens tested the work confirmed the hypothesis that properties of the bulk paste are the controlling factors in ionic diffusion through mortar.

Melt processable biomaterials for degradable surgical fixation devices

There are currently few biomaterials which combine controlled degradation rates with ease of melt processability. There are however, many applications ranging from surgical fixation devices to drug delivery systems which require such combination properties. The work in this thesis is an attempt to increase the availability of such materials. Polyhydroxybutyrate-polyhydroxyvalerate copolymers are a new class of potentially biodegradable materials, although little quantitative data relating to their in vitro and in vivo degradation behaviour exists. The hydrolytic degradation of these copolymers has been examined in vitro under conditions ranging from `physiological' to extremes of pH and elevated temperature. Progress of the degradation process was monitored by weight loss and water uptake measurement, x-ray diffractometry, optical and electron microscopy, together with changes in molecular weight by gel permeation chromatography. The extent to which the degradation mechanism could be modified by forming blends with polysaccharides and polycaprolactone was also investigated. Influence of the valerate content, molecular weight, crystallinity, together with the physical form of the sample, the pH and the temperature of the aqueous medium on the hydrolytic degradation was investigated. Its progress was characterised by an initial increase in the wet weight, with concurrent decrease in the dry weight as the amorphous regions of the polymer are eroded, thereby producing an increase in matrix porosity. With the polysaccharide blends, this initial rate is dramatically affected, and erosion of the polysaccharide from the matrix markedly increases the internal porosity which leads to the eventual collapse of the matrix, a process which occurs, but less rapidly, in the degradation of the unblended polyhydroxybutyrate-polyhydroxyvalerate copolymers. Surface energy measurement and goniophotometry proved potentially useful in monitoring the early stages of the degradation, where surface rather than bulk processes predominate and are characterised by little weight loss.

Characterisation and surface-profiling techniques for composite particles produced by dry powder coating in pharmaceutical drug delivery

The production of composite particles using dry powder coating is a one-step, environmentally friendly, process for the fabrication of particles with targeted properties and favourable functionalities. Diverse functionalities, such flowability enhancement, content uniformity, and dissolution, can be developed from dry particle coating. In this review, we discuss the particle functionalities that can be tailored and the selection of characterisation techniques relevant to understanding their molecular basis. We address key features in the powder blend sampling process and explore the relevant characterisation techniques, focussing on the functionality delivered by dry coating and on surface profiling that explores the dynamics and surface characteristics of the composite blends. Dry particle coating is a solvent- and heat-free process that can be used to develop functionalised particles. However, assessment of the resultant functionality requires careful selection of sensitive analytical techniques that can distinguish particle surface changes within nano and/or micrometre ranges.

Plant oils as fuels for compression ignition engines: a technical review and life-cycle analysis

As an alternative fuel for compression ignition engines, plant oils are in principle renewable and carbon-neutral. However, their use raises technical, economic and environmental issues. A comprehensive and up-to-date technical review of using both edible and non-edible plant oils (either pure or as blends with fossil diesel) in CI engines, based on comparisons with standard diesel fuel, has been carried out. The properties of several plant oils, and the results of engine tests using them, are reviewed based on the literature. Findings regarding engine performance, exhaust emissions and engine durability are collated. The causes of technical problems arising from the use of various oils are discussed, as are the modifications to oil and engine employed to alleviate these problems. The review shows that a number of plant oils can be used satisfactorily in CI engines, without transesterification, by preheating the oil and/or modifying the engine parameters and the maintenance schedule. As regards life-cycle energy and greenhouse gas emission analyses, these reveal considerable advantages of raw plant oils over fossil diesel and biodiesel. Typical results show that the life-cycle output-to-input energy ratio of raw plant oil is around 6 times higher than fossil diesel. Depending on either primary energy or fossil energy requirements, the life-cycle energy ratio of raw plant oil is in the range of 2–6 times higher than corresponding biodiesel. Moreover, raw plant oil has the highest potential of reducing life-cycle GHG emissions as compared to biodiesel and fossil diesel.

Potential for broad range multiplexing of fibre Bragg gratings in polymer optical fibres and operation in the 700-nm wavelength range

Refractive index and structural characteristics of optical polymers are strongly influenced by the thermal history of the material. Polymer optical fibres (POF) are drawn under tension, resulting in axial orientation of the polymer molecular chains due to their susceptibility to align in the fibre direction. This change in orientation from the drawing process results in residual strain in the fibre and also affects the transparency and birefringence of the material (1-3). PMMA POF has failure strain as high as over 100%. POF has to be drawn under low tension to achieve this value. The drawing tension affects the magnitude of molecular alignment along the fibre axis, thus affecting the failure strain. The higher the tension the lower the failure stain will be. However, the properties of fibre drawn under high tension can approach that of fibre drawn under low tension by means of an annealing process. Annealing the fibre can generally optimise the performance of POF while keeping most advantages intact. Annealing procedures can reduce index difference throughout the bulk and also reduce residual stress that may cause fracture or distortion. POF can be annealed at temperatures approaching the glass transition temperature (Tg) of the polymer to produce FBG with a permanent blue Bragg wave-length shift at room temperature. At this elevated temperature segmental motion in the structure results in a lower viscosity. The material softens and the molecular chains relax from the axial orientation causing shrinking of the fibre. The large attenuation of typically 1dB/cm in the 1550nm spectral region of PMMA POF has limited FBG lengths to less than 10cm. The more expensive fluorinated polymers with lower absorption have had no success as FBG waveguides. Bragg grating have been inscribed onto various POF in the 800nm spectral region using a 30mW continuous wave 325nm helium cadmium laser, with a much reduced attenuation coefficient of 10dB/m (5). Fabricating multiplexed FBGs in the 800nm spectral region in TOPAS and PMMA POF consistently has lead to fabrication of multiplexed FBG in the 700nm spectral region by a method of prolonged annealing. The Bragg wavelength shift of gratings fabricated in PMMA fibre at 833nm and 867nm was monitored whilst the POF was thermally annealed at 80°C. Permanent shifts exceeding 80nm into the 700nm spectral region was attained by both gratings on the fibre. The large permanent shift creates the possibility of multiplexed Bragg sensors operating over a broad range. -------------------------------------------------------------------------------------------------------------------- 1. Pellerin C, Prud'homme RE, Pézolet M. Effect of thermal history on the molecular orientation in polystyrene/poly (vinyl methyl ether) blends. Polymer. 2003;44(11):3291-7. 2. Dvoránek L, Machová L, Šorm M, Pelzbauer Z, Švantner J, Kubánek V. Effects of drawing conditions on the properties of optical fibers made from polystyrene and poly (methyl methacrylate). Die Angewandte Makromolekulare Chemie. 1990;174(1):25-39. 3. Dugas J, Pierrejean I, Farenc J, Peichot JP. Birefringence and internal stress in polystyrene optical fibers. Applied optics. 1994;33(16):3545-8. 4. Jiang C, Kuzyk MG, Ding JL, Johns WE, Welker DJ. Fabrication and mechanical behavior of dye-doped polymer optical fiber. Journal of applied physics. 2002;92(1):4-12. 5. Johnson IP, Webb DJ, Kalli K, Yuan W, Stefani A, Nielsen K, et al., editors. Polymer PCF Bragg grating sensors based on poly (methyl methacrylate) and TOPAS cyclic olefin copolymer2011: SPIE.

In situ studies of phase separation and crystallization directed by Marangoni instabilities during spin-coating

Results of a pioneering study are presented in which for the first time, crystallization, phase separation and Marangoni instabilities occurring during the spin-coating of polymer blends are directly visualized, in real-space and real-time. The results provide exciting new insights into the process of self-assembly, taking place during spin-coating, paving the way for the rational design of processing conditions, to allow desired morphologies to be obtained. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sustainable energy from paper industry wastes

Secondary fibre paper mills are significant users of both heat and electricity which is mainly derived from the combustion of fossil fuels. The cost of producing this energy is increasing year upon year. These mills are also significant producers of fibrous sludge and reject waste material which can contain high amounts of useful energy. Currently the majority of these waste fractions are disposed of by landfill, land-spread or incineration using natural gas. These disposal methods not only present environmental problems but are also very costly. The focus of this work was to utilise the waste fractions produced at secondary fibre paper mills for the on-site production of combined heat and power (CHP) using advanced thermal conversion methods (gasification and pyrolysis), well suited to relatively small scales of throughput. The heat and power can either be used on-site or exported. The first stage of the work was the development of methods to condition selected paper industry wastes to enable thermal conversion. This stage required detailed characterisation of the waste streams in terms of proximate and ultimate analysis and heat content. Suitable methods to dry and condition the wastes in preparation for thermal conversion were also explored. Through trials at pilot scale with both fixed bed downdraft gasification and intermediate pyrolysis systems, the energy recovered from selected wastes and waste blends in the form of product gas and pyrolysis products was quantified. The optimal process routes were selected based on the experimental results, and implementation studies were carried out at the selected candidate mills. The studies consider the pre-processing of the wastes, thermal conversion, and full integration of the energy products. The final stage of work was an economic analysis to quantify economic gain, return on investment and environmental benefits from the proposed processes.

Fixed bed downdraft gasification of paper industry wastes

The two main wastes generated from secondary fibre paper mills are rejects (composed mainly of plastics and fibres) and de-inking sludge, both of which are evolved from the pulping process during paper manufacture. The current practice for the disposal of these wastes is either by land-spreading or land-filling. This work explores the gasification of blends of pre-conditioned rejects and de-inking sludge pellets with mixed wood chips in an Imbert type fixed bed downdraft gasifier with a maximum feeding capacity of 10kg/h. The producer gases evolved would generate combined heat and power (CHP) in an internal combustion engine. The results show that as much as 80wt.% of a brown paper mill's rejects (consisting of 20wt.% mixed plastics and 80wt.% paper fibres) could be successfully gasified in a blend with 20wt.% mixed wood chips. The producer gas composition was 16.24% H, 23.34% CO, 12.71% CO 5.21% CH and 42.49% N (v/v%) with a higher heating value of 7.3MJ/Nm. After the removal of tar and water condensate the producer gas was of sufficient calorific value and flow rate to power a 10kWe gas engine. Some blends using rejects from other mill types were not successful, and the limiting factor was usually the agglomeration of plastics present within the fuel.

Effects of engine cooling water temperature on performance and exhaust emission characteristics of a multi-cylinder CI engine operated with Jatropha-Butanol blend

Renewable alternatives such as biofuels and optimisation of the engine operating parameters can enhance engine performance and reduce emissions. The temperature of the engine coolant is known to have significant influence on engine performance and emissions. Whereas much existing literature describes the effects of coolant temperature in engines using fossil derived fuels, very few studies have investigated these effects when biofuel is used as an alternative fuel. Jatropha oil is a non-edible biofuel which can substitute fossil diesel for compression ignition (CI) engine use. However, due to the high viscosity of Jatropha oil, technique such as transesterification, preheating the oil, mixing with other fuel is recommended for improved combustion and reduced emissions. In this study, Jatropha oil was blended separately with ethanol and butanol, at ratios of 80:20 and 70:30. The fuel properties of all four blends were measured and compared with diesel and jatropha oil. It was found that the 80% jatropha oil + 20% butanol blend was the most suitable alternative, as its properties were closest to that of diesel. A 2 cylinder Yanmar engine was used; the cooling water temperature was varied between 50°C and 95°C. In general, it was found that when the temperature of the cooling water was increased, the combustion process enhanced for both diesel and Jatropha-Butanol blend. The CO2 emissions for both diesel and biofuel blend were observed to increase with temperature. As a result CO, O2 and lambda values were observed to decrease when cooling water temperature increased. When the engine was operated using diesel, NOX emissions correlated in an opposite manner to smoke opacity; however, when the biofuel blend was used, NOX emissions and smoke opacity correlated in an identical manner. The brake thermal efficiencies were found to increase slightly as the temperature was increased. In contrast, for all fuels, the volumetric efficiency was observed to decrease as the coolant temperature was increased. Brake specific fuel consumption was observed to decrease as the temperature was increased and was higher on average when the biofuel was used, in comparison to diesel. The study concludes that the effects of engine coolant temperature on engine performance and emission characteristics differ between biofuel blend and fossil diesel operation. The coolant temperature needs to be optimised depending on the type of biofuel for optimum engine performance and reduced emissions.

Shaken not stirred:mixing semantics into XPDL

Ubiquitous computing requires lightweight approaches to coordinating tasks distributed across smart devices. We are currently developing a semantic workflow modelling approach that blends the proven robustness of XPDL with semantics to support proactive behaviour. We illustrate the potential of the model through an example based on mixing a dry martini.