Neste trabalho, foi avaliado o comportamento de alguns flavonóides e do adjuvante tecnológico celulose microcristalina (CMCr) no estado sólido, em relação ao tipo de interação e sua intensidade, quando existente, utilizando misturas físicas equiponderais e na proporção ponderal 1:2, respectivamente, através da calorimetria exploratória diferencial (DSC), análise termogravimétrica e espectroscopia no infravermelho (FTIR). A relação estrutura-propriedade de interação dos flavonóides estudados foi determinada nas possíveis interações sólido-sólido com a celulose microcristalina, correlacionando os padrões de hidroxilação nos anéis A, B e C dos flavonóides com: 1) a intensidade de variação (IV - %) entre as entalpias observada e esperada, 2) a energia do sistema conjugado do anel aromático relativa à banda I, 3) o pKa dos flavonóides e 4) os cálculos do campo de força da mecânica molecular 2 (MM2) para a energia de interação do sistema flavonóide-CMCr. Os flavonóides avaliados foram canferol, fisetina, luteolina, miricetina, morina e quercetina. Os resultados da DSC evidenciaram interações de natureza física do tipo ligações de hidrogênio, com variação de entalpia para todas as misturas dos flavonóides com a CMCr, mas que não puderam ser confirmadas por FTIR, devido à sobreposição de bandas com os flavonóides. O potencial de interação (PI) mostrou-se proporcional ao número de hidroxilas e apresentou a ordem de importância de posição e presença das hidroxilas nos anéis: B>C>A. A miricetina apresentou a menor energia do sistema conjugado do anel aromático relativa à banda I, relacionado ao maior PI entre os flavonóides estudados. Na avaliação do pKa dos flavonóides em relação à IV, não foi possível estabelecer uma correlação entre estas variáveis, não apresentando uma tendência de aumento ou diminuição do valor de pKa em relação ao aumento do PI. Os cálculos de MM2 para a energia de interação do sistema flavonóide-CMCr, considerando as dez interações propostas, demonstraram que a CMCr determinou a melhor orientação do flavonóide para obter a conformação de menor energia, não sendo possível estabelecer um padrão de conformação mais estável de interação para estes flavonóides. / In this work was evaluated the behavior of some flavonoids and of technological adjuvant microcrystalline cellulose (MCC) in solid state, in relation to the type of interaction and its intensity, when existing, using equiponderal physical mixtures and in 1:2 ratio, respectively, through of differential scanning calorimetry (DSC), thermogravimetric analysis and infrared spectroscopy (FTIR). Structure-property of interaction relation was determined to studied flavonoids in possible solid-solid interactions with MCC, correlating standard hydroxylation in A, B and C rings of flavonoids with: 1) intensity variation (IV-%) between observed and hoped enthalpies, 2) energy of the conjugated system of aromatic ring relative to band I, 3) pKa value of flavonoids and 4) molecular mechanics 2 (MM2) force field calculations for interaction energy of system flavonoid-MCC. Evaluated flavonoids were fisetin, kaempferol, luteolin, morin, myricetin and quercetin. DSC results evidenced physical interactions hydrogen bonds type, with enthalpy variation for all mixtures of flavonoids with MCC, but could not be confirmed by FTIR, due to overlapping with flavonoids bands. Interaction potential (IP) showed to be proportional to the number of hydroxyls and presented in order of importance of position and presence of hydroxyls in rings: B>C>A. Myricetin presented the lowest energy of the conjugated system of aromatic ring relative to band I, related with the highest IP among studied flavonoids. In the evaluation pKa value of flavonoids in relation to IV, it was not possible to establish a correlation between these variables, not presenting a trend of increase or decrease of pKa value in relation to the increase of IP. MM2 force field calculations for interaction energy of system flavonoid-MCC, considering ten proposed interactions, demonstrated that MCC determined the best orientation of flavonoids to get the lowest energy conformation, not being possible to establish the steadiest standard conformation of interaction for these flavonoids.

Neste trabalho, foi avaliado o comportamento de alguns flavonóides e do adjuvante tecnológico celulose microcristalina (CMCr) no estado sólido, em relação ao tipo de interação e sua intensidade, quando existente, utilizando misturas físicas equiponderais e na proporção ponderal 1:2, respectivamente, através da calorimetria exploratória diferencial (DSC), análise termogravimétrica e espectroscopia no infravermelho (FTIR). A relação estrutura-propriedade de interação dos flavonóides estudados foi determinada nas possíveis interações sólido-sólido com a celulose microcristalina, correlacionando os padrões de hidroxilação nos anéis A, B e C dos flavonóides com: 1) a intensidade de variação (IV - %) entre as entalpias observada e esperada, 2) a energia do sistema conjugado do anel aromático relativa à banda I, 3) o pKa dos flavonóides e 4) os cálculos do campo de força da mecânica molecular 2 (MM2) para a energia de interação do sistema flavonóide-CMCr. Os flavonóides avaliados foram canferol, fisetina, luteolina, miricetina, morina e quercetina. Os resultados da DSC evidenciaram interações de natureza física do tipo ligações de hidrogênio, com variação de entalpia para todas as misturas dos flavonóides com a CMCr, mas que não puderam ser confirmadas por FTIR, devido à sobreposição de bandas com os flavonóides. O potencial de interação (PI) mostrou-se proporcional ao número de hidroxilas e apresentou a ordem de importância de posição e presença das hidroxilas nos anéis: B>C>A. A miricetina apresentou a menor energia do sistema conjugado do anel aromático relativa à banda I, relacionado ao maior PI entre os flavonóides estudados. Na avaliação do pKa dos flavonóides em relação à IV, não foi possível estabelecer uma correlação entre estas variáveis, não apresentando uma tendência de aumento ou diminuição do valor de pKa em relação ao aumento do PI. Os cálculos de MM2 para a energia de interação do sistema flavonóide-CMCr, considerando as dez interações propostas, demonstraram que a CMCr determinou a melhor orientação do flavonóide para obter a conformação de menor energia, não sendo possível estabelecer um padrão de conformação mais estável de interação para estes flavonóides. / In this work was evaluated the behavior of some flavonoids and of technological adjuvant microcrystalline cellulose (MCC) in solid state, in relation to the type of interaction and its intensity, when existing, using equiponderal physical mixtures and in 1:2 ratio, respectively, through of differential scanning calorimetry (DSC), thermogravimetric analysis and infrared spectroscopy (FTIR). Structure-property of interaction relation was determined to studied flavonoids in possible solid-solid interactions with MCC, correlating standard hydroxylation in A, B and C rings of flavonoids with: 1) intensity variation (IV-%) between observed and hoped enthalpies, 2) energy of the conjugated system of aromatic ring relative to band I, 3) pKa value of flavonoids and 4) molecular mechanics 2 (MM2) force field calculations for interaction energy of system flavonoid-MCC. Evaluated flavonoids were fisetin, kaempferol, luteolin, morin, myricetin and quercetin. DSC results evidenced physical interactions hydrogen bonds type, with enthalpy variation for all mixtures of flavonoids with MCC, but could not be confirmed by FTIR, due to overlapping with flavonoids bands. Interaction potential (IP) showed to be proportional to the number of hydroxyls and presented in order of importance of position and presence of hydroxyls in rings: B>C>A. Myricetin presented the lowest energy of the conjugated system of aromatic ring relative to band I, related with the highest IP among studied flavonoids. In the evaluation pKa value of flavonoids in relation to IV, it was not possible to establish a correlation between these variables, not presenting a trend of increase or decrease of pKa value in relation to the increase of IP. MM2 force field calculations for interaction energy of system flavonoid-MCC, considering ten proposed interactions, demonstrated that MCC determined the best orientation of flavonoids to get the lowest energy conformation, not being possible to establish the steadiest standard conformation of interaction for these flavonoids.

Neste trabalho, foi avaliado o comportamento de alguns flavonóides e do adjuvante tecnológico celulose microcristalina (CMCr) no estado sólido, em relação ao tipo de interação e sua intensidade, quando existente, utilizando misturas físicas equiponderais e na proporção ponderal 1:2, respectivamente, através da calorimetria exploratória diferencial (DSC), análise termogravimétrica e espectroscopia no infravermelho (FTIR). A relação estrutura-propriedade de interação dos flavonóides estudados foi determinada nas possíveis interações sólido-sólido com a celulose microcristalina, correlacionando os padrões de hidroxilação nos anéis A, B e C dos flavonóides com: 1) a intensidade de variação (IV - %) entre as entalpias observada e esperada, 2) a energia do sistema conjugado do anel aromático relativa à banda I, 3) o pKa dos flavonóides e 4) os cálculos do campo de força da mecânica molecular 2 (MM2) para a energia de interação do sistema flavonóide-CMCr. Os flavonóides avaliados foram canferol, fisetina, luteolina, miricetina, morina e quercetina. Os resultados da DSC evidenciaram interações de natureza física do tipo ligações de hidrogênio, com variação de entalpia para todas as misturas dos flavonóides com a CMCr, mas que não puderam ser confirmadas por FTIR, devido à sobreposição de bandas com os flavonóides. O potencial de interação (PI) mostrou-se proporcional ao número de hidroxilas e apresentou a ordem de importância de posição e presença das hidroxilas nos anéis: B>C>A. A miricetina apresentou a menor energia do sistema conjugado do anel aromático relativa à banda I, relacionado ao maior PI entre os flavonóides estudados. Na avaliação do pKa dos flavonóides em relação à IV, não foi possível estabelecer uma correlação entre estas variáveis, não apresentando uma tendência de aumento ou diminuição do valor de pKa em relação ao aumento do PI. Os cálculos de MM2 para a energia de interação do sistema flavonóide-CMCr, considerando as dez interações propostas, demonstraram que a CMCr determinou a melhor orientação do flavonóide para obter a conformação de menor energia, não sendo possível estabelecer um padrão de conformação mais estável de interação para estes flavonóides. / In this work was evaluated the behavior of some flavonoids and of technological adjuvant microcrystalline cellulose (MCC) in solid state, in relation to the type of interaction and its intensity, when existing, using equiponderal physical mixtures and in 1:2 ratio, respectively, through of differential scanning calorimetry (DSC), thermogravimetric analysis and infrared spectroscopy (FTIR). Structure-property of interaction relation was determined to studied flavonoids in possible solid-solid interactions with MCC, correlating standard hydroxylation in A, B and C rings of flavonoids with: 1) intensity variation (IV-%) between observed and hoped enthalpies, 2) energy of the conjugated system of aromatic ring relative to band I, 3) pKa value of flavonoids and 4) molecular mechanics 2 (MM2) force field calculations for interaction energy of system flavonoid-MCC. Evaluated flavonoids were fisetin, kaempferol, luteolin, morin, myricetin and quercetin. DSC results evidenced physical interactions hydrogen bonds type, with enthalpy variation for all mixtures of flavonoids with MCC, but could not be confirmed by FTIR, due to overlapping with flavonoids bands. Interaction potential (IP) showed to be proportional to the number of hydroxyls and presented in order of importance of position and presence of hydroxyls in rings: B>C>A. Myricetin presented the lowest energy of the conjugated system of aromatic ring relative to band I, related with the highest IP among studied flavonoids. In the evaluation pKa value of flavonoids in relation to IV, it was not possible to establish a correlation between these variables, not presenting a trend of increase or decrease of pKa value in relation to the increase of IP. MM2 force field calculations for interaction energy of system flavonoid-MCC, considering ten proposed interactions, demonstrated that MCC determined the best orientation of flavonoids to get the lowest energy conformation, not being possible to establish the steadiest standard conformation of interaction for these flavonoids.

In the pharmaceutical industry, it is always important to have reproducible processes and raw materials of high quality to ensure good quality products. AstraZeneca, that is a leading manufacturer of different pharmaceuticals, works according to GMP to make sure that their processes deliver products of the same quality every time. A problem that has occurred at AstraZeneca is when a raw material is not properly understood and variations in the raw material affects the final product. Variations in drug release in one of AstraZeneca´s products, Product X, has been linked to the cushioning excipient Microcrystalline cellulose (MCC). Variations in drug release has been noticed during change from one batch of MCC to another. The aim of this study was to investigate which material attributes of MCC that contributes to variations in the final product. Particle size and moisture content were identified as critical material attributes (CMA´s) and were therefore chosen to be investigated more thoroughly. By variating particle size and moisture content during manufacturing of Product X, the influence of these attributes could be investigated using Design of Experiment (DoE). An additional experiment that compared two MCC batches from different suppliers was also performed during this study. The results from these experiments showed that the particle size and moisture content of MCC does affect the drug release. Large particles and high moisture content gave rise to a faster drug release compared to small particles and low moisture content that gave rise to a slower drug release. It is however hard to draw conclusions regarding how small differences in particle size and moisture content could affect the drug release.

[pt] A busca por materiais que não impactem negativamente o meio ambiente tem sido uma das prioridades de engenheiros que trabalham com materiais de construção. A emissão expressiva de CO2 na produção de cimento contribui para tal preocupação. Dentro deste cenário, soluções com emprego de nanotecnologia vêm chamando a atenção em diversas áreas por proporcionar novas soluções. O principal objetivo da presente tese é associar um material proveniente de uma fonte natural com benefícios provenientes da nanotecnologia a fim de modificar propriedades de pastas de cimento considerando seus aspectos químicos, físicos e mecânicos. A nanocelulose se apresenta como material proveniente de fonte renovável que apresenta propriedades atraentes aos materiais cimentícios, sendo assim uma opção a ser utilizada em conjunto com o cimento. Dentre os diversos tipos disponíveis, a celulose nanofibrilada (CNF) foi elencada para ser investigada neste trabalho. A celulose microcristalina (CMM) foi incluída nas investigações para possibilitar uma comparação direta entre as fibrilas da CNF e as partículas de CMM. O uso desses materiais celulósicos pode ser considerado recente e, com isso, existem ainda lacunas no que tange o entendimento dos seus efeitos em materiais cimentícios. Assim, a viabilidade da CNF e da CMM enquanto reforços em pastas de cimento foi avaliada por meio de ensaios de compressão e flexão. Os possíveis mecanismos responsáveis pelo efeito de ambas CMM e CNF foram estudados por meio de análises químicas e físicas. Por fim, foi realizada a caracterização das pastas reforçadas quanto à retração, total e autógena, e à reologia, nos regimes estático e dinâmico. Por conta dos impactos na trabalhabilidade promovidos pela inclusão de CNF, a mistura delas nas pastas de cimento foi facilitada com a adição de superplastificante, especialmente em porcentagens maiores que 0.050 por cento, em peso. A CMM e a CNF se mostraram eficazes em reforçar as pastas de cimento quanto a esforços de flexão e tração, levando ao aumento das respectivas resistências e módulos. Os resultados obtidos mostraram que a água presente no gel da CNF não está totalmente disponível como água de mistura por conta da morfologia e hidroficilidade das fibrilas. Observada uma certa combinação de porcentagem e fator água-cimento, a inclusão de CNF diminuiu a retração autógena das pastas. A inclusão de 0,040 por cento de NFC levou a resultados semelhantes aos da adição de CMM referente ao aumento da tensão de escoamento e da viscosidade. / [en] The seek for low environmental impact materials has become one of the priorities of construction building materials engineers. One of the reasons is the massive growing contribution of cement production industry in worldwide CO2 emissions. In this scenario, the dissemination of nanotechnology into varied areas is drawing attention for enabling new possibilities. The idea of the present thesis is to associate a material provided from a natural source with the potential benefits of nanotechnology to modify conventional cement pastes regarding their chemical, physical and mechanical aspects. Nanocellulose arises as an alternative that meets an eco-friendly source with remarkably properties expected from nanomaterials. There are different types of nano cellulosic materials that may be tailored to achieve desired compatibilities with varied cementitious materials. In this work, nanofibrillated cellulose (NFC) in the form of gel, and microcrystalline cellulose (MCC) particles were investigated, so a comparison could be traced between them. The use of both NFC and MCC in cementitious materials is recent and there are important gaps regarding their effect. For that reason, the feasibility of MCC and NFC to act as reinforcement on cement pastes was evaluated through compressive and flexural tests. Then, the possible mechanisms behind the effect of MCC and NFC on the microstructure of cement pastes were investigated through distinct chemical and physical analyses. Moreover, the total and autogenous shrinkage were characterized, as well as the dynamic and static rheological behaviors. Due to rheological modifications, the mixture of cement pastes with NFC was facilitated by a superplasticizer, especially for percentages higher than 0.050 percent wt. The MCC and NFC promoted the reinforcement of the cement pastes, regarding flexural and tensile stresses, increasing the composite strength and modulus. It was observed that he water present in the NFC gel is not totally available as mixing water due to the morphology and hydrophilicity of the fibrils. If associating certain levels of inclusions and water ratio, the NFC inclusion led to a decrease in autogenous shrinkage. The addition of 0.040 percent of NFC resulted in similar outcomes to 1.000 percent of MCC regarding their ability to increase yield stress and viscosity.

<p>Relationships between stresses during the drying process, particle structural and functional properties, and particle engineering by the drying process were addressed in this thesis. In the first part, the importance of the drying phase and the effect of the drying rate on the intragranular porosity of microcrystalline cellulose pellets were investigated. Differences in porosities of dried pellets could be explained by liquid-related differences in densification during convective drying rather than by differences in densification during wet agglomeration. An increased drying rate gave more porous pellets with a lower compression shear strength, and thereby stronger tablets. The next part dealt with modulation of solid-state stability and tabletting behaviour of amorphous lactose by incorporation of different polymers by spray drying. Increased content and molecular weight of poly(vinylpyrrolidone) (PVP) resulted in an increased resistance to crystallisation provoked by heat and moisture. The stabilising effect was even more evident after long-term storage. However, the glass transition temperature was almost unaffected and may, therefore, be questioned as a stability indicator for these types of materials. The presence of the polymers resulted in somewhat less deformable particles. Incorporation of PVP increased the compactability, whilst a surfactant decreased it, which could be shown to be related to differences in particle-particle adhesivity between the different particles. This thesis contributes to increased mechanistic understanding in the area of particle engineering that may lead to better prediction and optimisation of the functionality of pharmaceutical particles, which is of the utmost importance in the development and production of solid dosage forms.</p>

Relationships between stresses during the drying process, particle structural and functional properties, and particle engineering by the drying process were addressed in this thesis. In the first part, the importance of the drying phase and the effect of the drying rate on the intragranular porosity of microcrystalline cellulose pellets were investigated. Differences in porosities of dried pellets could be explained by liquid-related differences in densification during convective drying rather than by differences in densification during wet agglomeration. An increased drying rate gave more porous pellets with a lower compression shear strength, and thereby stronger tablets. The next part dealt with modulation of solid-state stability and tabletting behaviour of amorphous lactose by incorporation of different polymers by spray drying. Increased content and molecular weight of poly(vinylpyrrolidone) (PVP) resulted in an increased resistance to crystallisation provoked by heat and moisture. The stabilising effect was even more evident after long-term storage. However, the glass transition temperature was almost unaffected and may, therefore, be questioned as a stability indicator for these types of materials. The presence of the polymers resulted in somewhat less deformable particles. Incorporation of PVP increased the compactability, whilst a surfactant decreased it, which could be shown to be related to differences in particle-particle adhesivity between the different particles. This thesis contributes to increased mechanistic understanding in the area of particle engineering that may lead to better prediction and optimisation of the functionality of pharmaceutical particles, which is of the utmost importance in the development and production of solid dosage forms.

Plast- och kompositindustrin har växt i årtionden och den ständigt växande världen och ny teknik kräver ännu större mängder polymerkompositer för en mängd olika tillämpningar. Numera är de negativa miljöaspekterna av polymerproduktion och plastavfall kända, men trots detta är råoljafortfarande det primära råmaterialet för de flesta polymerer. Att hitta biobaserade material medtillräckliga egenskaper för att ersätta de fullt syntetiska materialen är avgörande för en hållbarutveckling. Detta examensarbete studerar både glasfiber och mikrokristallin cellulosaarmerade biooljebaserade polyamider, samt undersöker hur de kan kompatibiliseras, deras mekaniska egenskaper samt användbarheten för additiv tillverkning. Kompatibilisering är en viktig aspekt när två föreningar blandas för att göra en komposit. Enlämplig kompatibilisator kommer att förbättra vidhäftningen vid gränsytan mellan armeringsmaterialet och polymermatrisen och därmed öka de mekaniska egenskaperna hos materialet. Glasfiber / polyamid-kompositen kompatibiliserades med vinyltrimetoxisilan, medanmikrokristallin cellulosa / polyamid-kompositen kompatibiliserades med 4,4'-difenylmetandiiisocyanat. Båda kompositerna analyserades för att erhålla information om termiska, mekaniska och reologiska egenskaper. Yt- och sprickmorfologin undersöktes också. Resultaten indikerar att armeringen resulterade i förbättrade mekaniska egenskaper, även om den önskade kompatibiliseringen inte erhölls i experimentet. Det mest uppmuntrande resultatet var att den biobaserade cellulosaarmeringen förbättrade de mekaniska egenskaperna. Genom visuell undersökning fanns den helt biobaserade polymerkompositen vara mjukare än den glasfiberarmerade. Framtidsutsikterna visar att det finns vissa problem att ta itu med och övervinna för att dessa material ska göras lämpliga för additiv tillverkning. Nyckeln är att hitta en kompatibilisator som tålupprepad bearbetning vid höga temperaturer. För att upprätthålla enhetliga egenskaper krävskorrekt spridning av armeringsmaterialet, vilket uppnås genom att optimera tillverkningsmetoden. Dessutom är cellulosa benägen att termisk nedbrytning, så behandlingstemperaturerna för både armeringsmaterialet och polymermatrisen bör övervägas noggrant. / Plastics and composites have been a growing industry for decades, and the always growing worldand new technologies demand even greater amounts of polymeric composites for a variety ofapplications. Nowadays the negative environmental aspects of polymer production and plastic waste are known, but despite that crude oil is still the primary material for most polymers. Finding biobased materials with sufficient properties to replace the fully synthetic ones is crucial in sustainable development. This master’s thesis studies both glass fiber and microcrystalline cellulose reinforcedbio-oil based polyamide, how they could be compatibilized, the mechanical properties and applicability for additive manufacturing. Compatibilization is an important aspect when two compounds are mixed to make a composite. A proper compatibilizer will enhance the interfacial adhesion between the reinforcement and matrix, thus increasing the mechanical properties of the material. The glass fiber/polyamide11 composite was compatibilized with vinyltrimethoxysilane, and the microcrystalline cellulose/polyamide11 composite was compatibilized with 4,4'-diphenylmethane diisocyanate. Both composites were analyzed to obtain information about thermal, mechanical, and rheological properties. The surface and fracture morphology are examined, as well.The results indicate that reinforcing resulted to enhanced mechanical properties, even though the desired compatibilization was not acquired in the experiment. The most encouraging result was that the bio-based cellulose reinforcement enhanced mechanical properties, by visual examination thefully bio-based polymeric composite was found to be more ductile than the glass fiber reinforcedone. For future prospect, there are few issues to be addressed and overcome for these materials to bemade suitable for additive manufacturing. The key is finding a compatibilizer that can withstand high processing temperatures repeatedly. Maintaining uniform properties requires proper dispersion of reinforcement, which is achieved by optimizing the manufacturing method. In addition, cellulose is prone to thermal degradation, so the processing temperatures for both reinforcement and matrix should be considered carefully. / Muovit ja komposiitit ovat jo vuosikymmenien ajan ollut kasvava teollisuuden ala, ja alatikehittyvä maailma sekä uudenlainen teknologia vaatii entistä enemmän polymeerikomposiittejaerilaisiin käyttökohteisiin. Nykyään polymeerituotannon ja käytöstä poistuvien muovituotteidennegatiivisista ympäristövaikutuksista ollaan tietoisia. Tästä huolimatta raakaöljy on pääraaka-ainepolymeerien valmistuksessa. Ympäristövaikutusten minimoimiseksi olisi tärkeää löytääbiopohjaisia materiaaleja, jotka ominaisuuksiensa puolesta ovat riittäviä korvaamaan täysinsynteettisiä materiaaleja. Tässä työssä on tutkittu sekä lasikuidulla että mikrokiteisellä selluloosallavahvistetun bioöljypohjaisen polyamidin kompatibilisointia ja mekaanisia ominaisuuksia, sekäkyseisten komposiittien soveltuvuutta materiaalia lisääviin valmistusmenetelmiin.Kompatibilisaatio on tärkeää, kun yhdistetään kaksi eri komponenttia yhdeksikomposiittimateriaaliksi. Sen tarkoituksena on vahvistaa molekyylien rajapinnan adheesiotalujitteen ja sidemassan välillä, jolloin materiaalin mekaaniset ominaisuudet paranevat. Lasikuidullalujitettujen polyamidikomposiittien kompatibilisointiin käytettiin vinyylitrimetoksisilaanilla jamikrokiteisellä selluloosalla lujitettu polyamidikomposiitti kompatibilisoitiin 4,4'-difenyylimetaanidi-isosyanaatilla. Molempien komposiittien termiset, mekaaniset ja reologiset ominaisuudetarvioitiin. Lisäksi tutkittiin pinnan ja murtumakohdan morfologiaa.Tulokset osoittavat, että polymeerin lujittaminen parantaa mekaanisia ominaisuuksia, vaikkatavoiteltua kompatibilisaatioita materiaalien välillä ei tapahtunutkaan. Työn lupaavin tulos olibiopohjaisen mikrokiteisen selluloosan tuoma parannus materiaalin kestävyysominaisuuksille.Etenkin silmämääräisesti tarkastellessa täysin biopohjainen polymeerikomposiitti oli taipuisampaakuin lasikuidulla lujitettu komposiitti.Muutamaan asiaan tulee kiinnittää erityisesti huomiota, jos tämänkaltaisia materiaaleja halutaankäyttää materiaalia lisäävissä menetelmissä. Tärkeintä on löytää kompatibilisoija, joka kestääkorkeita lämpötiloja toistuvasti. Lujitteen tasainen dispersio on tärkeää, jotta saadaan aikaantasaista laatua ja ominaisuudet ovat samanlaiset koko materiaalissa. Tämä saavutetaanvalmistusmenetelmän optimoinnilla. Lisäksi tulee ottaa huomioon selluloosan taipumus termiseenhajoamiseen, jolloin sekä lujitteen että sidemassan prosessointilämpötilat tulisi ollasamansuuruiset.

The twin screw extrusion technique has been explored to produce lyotropic liquid crystal coated powder precursor by exploiting Pluronic F127 thermoreversible gelation property to get powder precursor without granular aggregates or with less compacted granular aggregates. The highly soluble chlorpheniramine maleate loaded in Pluronic F127 solution coated MCC particles prepared through twin screw extrusion was examined to produce the cubic phase (gel) for the development of controlled release formulation and for coating of very fine particles which cannot be achieved by traditional bead coaters. Controlled release formulations are beneficial in reducing the frequency of administration of highly soluble drugs having short half life and also to address the problem of polypharmacy in old age patients by reduction of dosage frequency. An unusual refrigerated temperature (5 C) profile for twin screw extrusion was selected based on the complex viscoelastic flow behaviour of Pluronic F127 solution which was found to be highly temperature sensitive. The Pluronic F127 solution was found to be Newtonian in flow and less viscoelastic at low temperature, such that low temperature (5 C) conditions were found to be suitable for mixing and coating the MCC particles to avoid compacted aggregates. At higher temperatures (35-40 C) Pluronic F127 solution exhibited shear thinning and prominent viscoelasticity, properties which were exploited to force CPM containing Pluronic F127 solution to stick over the MCC surface. This was achieved by elevating the temperature of the last zone of the extrusion barrel. It was found that to avoid compacted aggregates the MCC must be five times the weight of the Pluronic F127 solution and processed at a screw speed of 400 RPM or above at refrigerated temperature. Processing was not found to be smooth at ambient temperature with frictional heat and high torque generation due to significant compaction of coated particles which can be attributed to the elastic behaviour of Pluronic F127 solution at temperatures between ambient to typical body temperature. PLM images confirmed the cubic phase formation (gel) by Pluronic F127 coating which was found to be thick with maximum Pluronic F127 concentration (25%). SEM images showed smoothing of surface topography, and stretching and elongation of MCC fibres after extrusion which is indicative of coating through extrusion processing. Plastic deformation was observed for the lower Pluronic F127 concentration and higher MCC proportions. There was a significant decrease in work done for cohesion by the powder flow analyser observed in the batches with more aggregates compared with batches with least aggregates. A regression analysis study on factorial design batches was conducted to investigate the significant independent variables and their impact on dependent variables for example % torque, geometric mean diameter and work done for cohesion, and to quantitatively evaluate them. From the regression analysis data it was found that the coefficient of determination for all three dependent variables was in the range of 55-62%. The pharmaceutical performance of the prepared coated LLC precursor through twin screw extrusion in terms of controlled release was found to be very disappointing. Almost 100% chlorpheniramine maleate was released within 10-15mins, defined as providing burst release. The MDSC method was developed within this work to detect Pluronic F127 solution cubic phase formation. The MDSC method was developed to consider sample size, effect of heating and cooling, sample heat capacity, and the parameters for highest sensitivity which can be followed by sample accurately without the phase lag to produce accurate repeatable results.