This thesis investigates the use, safety and regulation of the plasticisers, epoxidised soya bean oil (ESBO), acetyl tributyl citrate (ATBC) and di-(2-ethylhexyl) adipate (DEHA), which are used in food contact plastics. The thesis analyses the scientific evidence concerning the toxicity and migration of these plasticisers and the selection and interpretation of that evidence by relevant national and international expert committees and organisations in the UK and EC. The history of the control of these plasticisers is also examined in the context of an analysis of the general control of this sector in the UK and the EC from the 1950s to the 1990s. This investigation is located against the background of a review of the literature on the role that science can play in the policymaking process, and how social, political and economic factors may be structured into the process of expert evaluation of scientific evidence and risk assessment. The complex details of the chosen examples provide evidence that there are considerable uncertainties concerning the safety of these plasticisers. In the absence of adequate evidence of safety, it is concluded that historically, the benefit of the doubt has been consistently awarded in favour of the continued use of these plasticisers rather than in the cautious protection of public health. The further conclusion is drawn that the policy-process has been generally inadequate in this field in order to ensure adequate protection of public health. Evidence is presented which shows that the outcome of expert evaluation and policy-making in this field can be related to assumptions that have been made which have an identifiable political and economic basis. It is therefore concluded that there is a case for changes in the policy-making institutions and processes in order more effectively to protect public health.

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Les polymères ferroélectriques et plus récemment les matériaux électrostrictifs ont attiré l’attention de la communauté scientifique en raison de leur capacité de conversion d’une excitation électrique en une réponse mécanique et vice versa. La synergie entre les propriétés électro actives de ces polymères et leurs propriétés physico-chimiques intrinsèques (souplesse, légèreté, grande résistance mécanique, facilité de mise en œuvre etc.) en font des candidats de choix pour des applications de types capteurs et actionneurs souples. Cette thèse vise à déterminer de façon systématique le comportement électromécanique des terpolymères P (fluorure de vinylidène-trifluoréthylène-chlorotrifluoroéthylène) [P (VDF-TrFE-CTFE)] par des techniques de cristallisation et de technologies additives et entend étendre ces terpolymères à l'application des dispositifs de type capteur de force électromécanique. L'influence du traitement thermique sur la réponse électromécanique et la microstructure des terpolymères a d'abord été étudiée. Il a été mis en évidence que la déformation électrostrictive transversale S31 pour chaque terpolymère traité thermiquement suit une loi quadratique avec le champ électrique. Par ailleurs il a été démontré que la déflexion d’un actionneur unimorphe est maximisée pour une fraction de phase cristalline de 39,3%. La dynamique moléculaire des terpolymères cristallisés a également été étudiée par spectroscopie diélectrique à large bande. Une dynamique segmentaire contrainte a été observée dans le terpolymère contenant la fraction cristalline la plus élevée pour laquelle une distribution étroite du temps de relaxation a été mise en évidence. En outre, il a été démontré que l’ajout d’agent plastifiant permet d’augmenter de manière significative la réponse électromécanique des terpolymères fluorés, ouvrant la voie vers de nouveaux matériaux électrostrictifs hautes performances fonctionnant sous faible champ électrique. De plus, la réponse diélectrique et électromécanique accrue du terpolymère dopé a été étudiée par microscope à force atomique et spectroscopie diélectrique dynamique. Ces analyses ont permis de lier l’augmentation de la réponse électromécanique de ces mélanges à un effet de polarisation interfaciale intensifié lors de l’augmentation de mobilité moléculaire de la phase amorphe rigide de ces terpolymères fluorés. Enfin, des dispositifs électromécaniques basés sur le polymère ferroélectrique P (VDF-TrFE) et le terpolymère électrostrictif P (VDF-TrFE-CTFE) ont été élaborés. Un procédé de fabrication additive utilisant la technologie d'impression jet d'encre a permis de concevoir et valider la faisabilité de réalisation de capteurs de force dynamique. Il a alors été démontré que les propriétés pseudo-piézoélectriques du terpolymère électrostrictif sont équivalentes à celles du copolymère ferroélectrique pour un faible champ électrique de biais de 7,5 V /μ / Electromechanical coupling effect has been paid the increasing attention due to ability to realize conversion between electric excitation and mechanical response and vice versa. Thanks to their flexibility, light weight, relatively low mechanical strength, ease of processability into large-area films, and ability to be molded into desirable geometric dimensions, polymers materials which possess an electromechanical coupling effect have been emerging recently. This thesis aims to systematically determine the electromechanical behavior of the P(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene) [P(VDF-TrFE-CTFE)] terpolymers via crystallization and additive technology approaches and intend to extend such terpolymers to the electromechanical force sensor devices application. The influence of the thermal processing on the electromechanical response and microstructure of the terpolymers were firstly investigated. Cantilever unimorph bending measurement found the tip displacement δ and transverse strain S_31 for each thermally treated terpolymer followed a quadratic correlation with the electric field. δ was maximized at a 39.3% crystal content, instead of S_31 peaking at lowest crystal content, showing an exponential decay against the crystal fraction increasing. The dynamics of crystallized terpolymers were additionally studied via broadband dielectric spectroscopy. Constrained segmental dynamics was observed in the terpolymer containing the highest crystal fraction for which a narrow relaxation time distribution was found. Moreover, the enhanced dielectric and electromechanical response of DEHP doped terpolymer were interpreted via morphology microstructure and molecular mobility analysis. Interfacial polarization shifted to the high frequency by one decade because of dopant DEHP. Finally, electromechanical devices based on ferroelectric P(VDF-TrFE) and electrostrictive P(VDF-TrFE-CTFE) towards the dynamic force sensor implementation were designed and fabricated via inkjet printing technology. The bias electric field for terpolymer sensor was much lower than the poling electric field for a copolymer sensor. And the piezoelectric properties equivalent to the corresponding copolymer sensor can be obtained for a bias as low as 7.5 V/μ

Compression of coated pellets is a practical alternative to capsule filling. The current practice is to add cushioning agents to minimize the stress on the coated pellets. Cushioning agents however add bulkiness and reduce the overall drug loading capacity. In this study, we investigated the performance of compressed coated pellets with no cushioning agent to evaluate the feasibility of predicting the coat behaviour using thermo-mechanical and rheological analysis techniques. Different coating formulations were made of ethyl cellulose (EC) as a coating polymer and two different kinds of additives were incorporated into the polymeric coating solution. Triethyl Citrate (TEC) and Polyethylene glycol 400(PEG400) were used as plasticizers at different levels to the coating formulations (10%, 20%, 30%). Thermal, mechanical and rheological measurements of the coating film formulations were achieved to investigate the effect of plasticizers. Thermal gravimetric analysis results (TGA) showed higher residual moisture content in films plasticised with PEG 400 compared to their TEC counterparts. Differential Scanning Calorimetry (DSC), Dynamic Mechanical Analysis (DMA) and Parallel Plate Shear Rheometer (PPSR) were used to study the influence of the level and type of plasticisers incorporated in coating film formulation on the performance of the coating film. In this study, both DSC and DMA were used to investigate the Tg for each film coating formulation in order to evaluate the effect of the additives. In general DMA results for the Tg value of the films were always higher by 10-20% than those measured by the DSC. Furthermore, clamp size and the frequency of the oscillation have an influence on the evaluation of Tg. Complex viscosity for different coating film formulations revealed that the shear hinning gradient changes with temperature and plasticiser type and concentration. The value of complex viscosity from DMA and PPSR exhibits power law behaviour. The rheological moduli were indirectly affected by the level of plasticiser. There was a discrepancy between the complex viscosity results obtained from both DMA and PPSR at similar temperature but they follow the same trend. The non plasticized polymer showed a 10 time higher complex viscosity values when measured by DMA over that measured by PPSR. The difference was smaller in plasticized films but it was not consistent. Therefore a consistent coefficient to correlate the DMA and PPSR couldn’t be accurately determined Coated pellets were compressed and key process parameters were evaluated. The obtained results revealed that the coating thickness has a significant effect on the release profile of the final products. It was found that by increasing the coating film thickness, the percentage released decreased. Also the compression force has lower influence on the drug release profile, while the dwell time has very low effect on the percentage release from the final products. Optimum release profile was obtained at a coating level of 5.5% w/w and a compression force of 4700N In conclusion, the elasticity of the plasticised EC films in this study meant that the internal stress is not dissipated during compression and the dwell time range that was used in this experiment. Increasing the thickness therefore was necessary to enhance the strength of the film and avoid cracking. The mechanical and rheological profiling was helpful therefore to understand the behaviour of the coated pellets and predict the film properties at various steps of the process of coating and compression (i.e., various shear rate regimes). Experimental design approach to studying the key process and formulation parameters helped identify the optimum values for the process.

Applications of Hot Melt Extrusion (HME) in pharmaceuticals have become increasingly popular over the years but nonetheless a few obstacles still remain before wide scale implementation. In many instances these improvements are related to both processing and product performance. It is observed that HME process optimisation is majorly focused on the active pharmaceutical ingredient's (API) properties. Characterising polymeric properties for their suitability in HME should be equally studied since the impact of excipients on both product and process performance is just as vital. In this work, two well-established cellulose ester derivatives: Hydroxy Propyl Methyl Cellulose Acetate Succinate (HPMCAS) and Hydroxy Propyl Methyl Cellulose Phthalate (HPMCP) are studied for their HME suitability. Their thermal, thermodynamic, rheological, thermo-chemical and degradation kinetic properties were evaluated with model plasticisers and APIs. It was found the thermal properties of HPMCP are severely compromised whereas HPMCAS is more stable in the processing zone of 150 to 200 °C. Thermodynamic properties revealed that both polymers share an important solubility parameter range (20-30 MPa P1/2P) where the majority of plasticisers and BCS class II APIs lie. Thus, greater miscibility/solubility can be expected. Further, the processability of these two polymers investigated by rheometric measurements showed HPMCAS possesses better flow properties than HPMCP because HPMCP forms a weak network of chain interactions at a molecular level. However, adding plasticisers such as PEG and TEC the flow properties of HPMCP can be tailored. The study also showed that plasticisers have a major influence on thermo-chemical and kinetic properties of polymers. For instance, PEG reduced polymer degradation with reversal in kinetic parameters whereas blends of CA produced detrimental effects and increased polymer degradation with reduction in onset degradation temperatures. Further, both polymers are observed to be chemically reactive with the APIs containing free -OH, -SOR2RN- and -NH2 groups. Finally, these properties prove that suitability of HPMCP is highly debated for HME and demands great care in use while that of HPMCAS is relatively better than HPMCP in many instances.

Applications of Hot Melt Extrusion (HME) in pharmaceuticals have become increasingly popular over the years but nonetheless a few obstacles still remain before wide scale implementation. In many instances these improvements are related to both processing and product performance. It is observed that HME process optimisation is majorly focused on the active pharmaceutical ingredient's (API) properties. Characterising polymeric properties for their suitability in HME should be equally studied since the impact of excipients on both product and process performance is just as vital. In this work, two well-established cellulose ester derivatives: Hydroxy Propyl Methyl Cellulose Acetate Succinate (HPMCAS) and Hydroxy Propyl Methyl Cellulose Phthalate (HPMCP) are studied for their HME suitability. Their thermal, thermodynamic, rheological, thermo-chemical and degradation kinetic properties were evaluated with model plasticisers and APIs. It was found the thermal properties of HPMCP are severely compromised whereas HPMCAS is more stable in the processing zone of 150 to 200 °C. Thermodynamic properties revealed that both polymers share an important solubility parameter range (20-30 MPa P1/2P) where the majority of plasticisers and BCS class II APIs lie. Thus, greater miscibility/solubility can be expected. Further, the processability of these two polymers investigated by rheometric measurements showed HPMCAS possesses better flow properties than HPMCP because HPMCP forms a weak network of chain interactions at a molecular level. However, adding plasticisers such as PEG and TEC the flow properties of HPMCP can be tailored. The study also showed that plasticisers have a major influence on thermo-chemical and kinetic properties of polymers. For instance, PEG reduced polymer degradation with reversal in kinetic parameters whereas blends of CA produced detrimental effects and increased polymer degradation with reduction in onset degradation temperatures. Further, both polymers are observed to be chemically reactive with the APIs containing free -OH, -SOR2RN- and -NH2 groups. Finally, these properties prove that suitability of HPMCP is highly debated for HME and demands great care in use while that of HPMCAS is relatively better than HPMCP in many instances.