As folhas de Maytenus ilicifolia são amplamente utilizadas na medicina tradicional brasileira no tratamento de distúrbios gástricos. Após a comprovação de sua eficácia e segurança, a referida droga vegetal tem sido objeto de diversos estudos com a finalidade de estabelecer parâmetros para o controle de qualidade. Neste sentido, foi avaliada a viabilidade do desenvolvimento de um método analítico fundamentado na precipitação de taninos empregando povidona como agente seqüestrante. Os dados revelaram que a remoção de taninos em solução é satisfatória quando empregada a povidona insolúvel. Foi observado que o polímero também é capaz de precipitar outros polifenóis além dos taninos presentes na solução extrativa de M. ilicifolia. Entretanto, as interações do polímero ocorrem preferencialmente com os derivados catéquicos. Adicionalmente foi desenvolvido e validado um método por CLAE para separação e quantificação de catequina e epicatequina em produtos derivados de M. ilicifolia. Não foram detectadas variações nas áreas dos picos ou nos tempos de retenção durante os ensaios de avaliação do método, sugerindo que as condições cromatográficas empregadas são satisfatórias. Para viabilizar a preparação de produto seco por aspersäo (PSA) em torre de secagem piloto munida de aspersor rotatório, foi necessária a concentração da solução extrativa. A operação foi realizada sob pressão reduzida até alcangar um teor de sólidos mínimo de 15 % (m/m). A operação de secagem da solução concentrada apresentou rendimento de 90 % e o PSA obtido apresentou partículas esféricas, com superfície rugosa e tamanho médio de 22,5 um. A caracterização tecnológica do material revelou que as suas propriedades tecnológicas, tais como, densidades, compressibilidade e fluxo, foram incrementadas quando comparados com o produto preparado em equipamento de bancada. Entretanto, estas modificações não foram suficientes para viabilizar sua compressão direta. Assim sendo, o material foi compactado em máquina de comprimir e em rolos para produção de grânulos. A análise do perfil compressional do PSA e dos granulados, empregando o modelo de Heckel, revelou que o aumento da força de compactação durante a operação de granulação foi o principal responsável pela diminuição no potencial de deformação plástica dos grânulos. Como conseqüência, a recompressão dos grânulos em máquina de comprimir originou compactos com dureza inferior àqueles preparados diretamente do complexo farmacêutico. Enquanto o PSA apresentou reduzida tendência ao rearranjo particular nos estágios iniciais da compressão, os grânulos sofreram intensa reacomodação decorrente da fragmentação e formação de novas pontes, assumindo comportamento plástico em pressões de compressão mais elevadas. Por fim, comprimidos contendo teor elevado de granulado de PSA foram preparados utilizando como adjuvantes a celulose microcristalina, o dióxido de silício coloidal e a croscarmelose sódica. A influência da concentração de dióxido de silício coloidal e croscarmelose sódica na formulação, sobre as respostas de dureza, friabilidade e tempo de desintegração dos comprimidos foram avaliadas através de um Desenho Composto Central. Os dados experimentais foram analisados estatisticamente, utilizando os modelos matemáticos para gerar superfícies de resposta. Os resultados indicaram que a concentração de dióxido de silício coloidal foi inversamente relacionada às respostas de dureza e friabilidade, enquanto que a concentração de croscarmelose sódica foi a principal responsável pela redução no tempo de desintegração. As condições ótimas foram selecionadas através da sobreposição dos gráficos, buscando uma formulação com menor tempo de desintegração, menor friabilidade e o máximo de dureza. A formulação eleita deve conter 1,2 % (m/m) de dióxido de silício coloidal e 5,0 % (m/m) de croscarmelose sódica. Nestas condições os comprimidos apresentaram dureza de 107,9 N, friabilidade de 0,56 % (m/m) e desintegração máxima em 6,8 min. / The leaves of Maytenus ilicifolia are widely used within the traditional Brazilian medicine due to its properties against gastric disorders. Once proved its efficacy and safety, this vegetable drug has been the object of several studies to establish the basis for quality control. Taking this into consideration, it was necessary to evaluate the feasibility of developing an analytical method based on the precipitation of tannins, by using polyvinylpyrrolidone for precipitation. The data have shown that the removal of the tannins in solution was successful when insoluble polyvinylpyrrolidone was used. Hereby it was observed that the polymer has also the ability to precipitate other polyphenols besides the tannins from the aqueous solution of M. ilicifolia. However, the interactions of the polymer happened mostly with the condensed tannins. Further it was developed and also validated an HPLC method to separate and quantify catechin and epicatechin present in aqueous extracts of M. ilicifolia. No significant variations of peak areas or retention times were observed when the evaluation of the method was executed, showing satisfactory chromatographic conditions. In order to make a spray dried extract (SDE) using a spray-drier fitted out with a rotary atomizer, it was necessary to concentrate the extractive solution. This operation had been performed under reduced pressure until a content of 15 % solids was achieved. The drying of the concentrated solution lead to a yield of 90 %, and the obtained SDE presented spherical particles, which have a rough surface and a mean particle size of 22,51.1.m. The technological characterization of the SDE showed that attributes such as densities (tap and bulk), compressibility and flow, have been improved when compared to the product prepared using a mini spray-drier supplied with a pneumatic nozzle. However, these modifications were not enough to enable its direct compression. Therefore, the material was compacted to produce granules after slugging or roller compaction, The compressional analysis of the SDE and each granule batch using the Heckel equation proved that the increase in the compaction force once processing the granulation was the main factor to reduce the material's ability to undergo plastic deformation. Consequently, the recompression of the granules in a tablet press led to compacts with a lower crushing strength compared to that prepared by direct compression of the pharmaceutical complex. Whereas the SDE has shown a reduced tendency to particle rearrangement at early stage of compression, the granules showed an intense fragmentation and rebound behavior, presenting a plastic behavior when higher compaction pressures were used. Finally, tablets containing a high dose of granulated spray dried extract of M. ilicifolia were prepared by using the following excipients: microcrystalline cellulose (filler/binder), colloidal silicon dioxide (glidant and moisture adsorber) and cross-linked carboxymethylcellulose (disintegrant). The influences of colloidal silicon dioxide (CSD) and cross-linked carboxymethylcellulose (CMC-Na) on the tablet hardness, disintegration time and friability were evaluated by a central composite design. The data were analyzed statistically and mathematical models were used to create response surfaces. The results have indicated that the concentration of CSD shows an inverse relation to the responses of hardness and friability, while the concentration of CMC-Na was the most important factor that caused a reduction of the time necessary for total disintegration. The optimal conditions for processing were chosen by the overlapping of graphics, taking into consideration that the formulation should present a minimum of disintegration time, lower friability and a maximum of hardness. Thus, it was found that the best formulation should have a content of 1.2% (w/w) of CSD and 5.0% (w/w) of CMC-Na. Regarding these conditions, the tablets have shown a hardness of 107.9 N, friability of 0.56% (w/w) and a disintegration time of 6.8 min.

Roll compaction is a continuous process commonly used in the pharmaceutical industry for dry granulation of moisture and heat sensitive powder blends. It is intended to increase bulk density and improve flowability. Roll compaction is a complex process that depends on many factors, such as feed powder properties, processing conditions and system layout. Some of the variability in the process remains unexplained. Accordingly, modeling tools are needed to understand the properties and the interrelations between raw materials, process parameters and the quality of the product. It is important to look at the whole manufacturing chain from raw materials to tablet properties. The main objective of this thesis was to investigate the impact of raw materials, process parameters and system design variations on the quality of intermediate and final roll compaction products, as well as their interrelations. In order to do so, we have conducted a series of systematic experimental studies and utilized chemometric tools, such as design of experiments, latent variable models (i.e. PCA, OPLS and O2PLS) as well as mechanistic models based on the rolling theory of granular solids developed by Johanson (1965). More specifically, we have developed a modeling approach to elucidate the influence of different brittle filler qualities of mannitol and dicalcium phosphate and their physical properties (i.e. flowability, particle size and compactability) on intermediate and final product quality. This approach allows the possibility of introducing new fillers without additional experiments, provided that they are within the previously mapped design space. Additionally, this approach is generic and could be extended beyond fillers. Furthermore, in contrast to many other materials, the results revealed that some qualities of the investigated fillers demonstrated improved compactability following roll compaction. In one study, we identified the design space for a roll compaction process using a risk-based approach. The influence of process parameters (i.e. roll force, roll speed, roll gap and milling screen size) on different ribbon, granule and tablet properties was evaluated. In another study, we demonstrated the significant added value of the combination of near-infrared chemical imaging, texture analysis and multivariate methods in the quality assessment of the intermediate and final roll compaction products. Finally, we have also studied the roll compaction of an intermediate drug load formulation at different scales and using roll compactors with different feed screw mechanisms (i.e. horizontal and vertical). The horizontal feed screw roll compactor was also equipped with an instrumented roll technology allowing the measurement of normal stress on ribbon. Ribbon porosity was primarily found to be a function of normal stress, exhibiting a quadratic relationship. A similar quadratic relationship was also observed between roll force and ribbon porosity of the vertically fed roll compactor. A combination of design of experiments, latent variable and mechanistic models led to a better understanding of the critical process parameters and showed that scale up/transfer between equipment is feasible.

Malaria affects about forty percent of the world’s population. Annually more than 1.5 million fatalities due to malaria occur and parasite resistance to existing antimalarial drugs such as mefloquine has already reached disturbingly high levels in South-East Asia and on the African continent. Consequently, there is a dire need for new drugs or formulations in the prophylaxis and treatment of malaria. Artesunate, an artemisinin derivative, represents a new category of antimalarials that is effective against drug-resistant Plasmodium falciparum strains and is of significance in the current antimalarial campaign. As formulating an ACT double fixed-dose combination is technically difficult, it is essential that fixed-dose combinations are shown to have satisfactory ingredient compatibility, stability, and dissolution rates similar to the separate oral dosage forms. Since the general deployment of a combination of artesunate and mefloquine in 1994, the cure rate increased again to almost 100% from 1998 onwards, and there has been a sustained decline in the incidence of Plasmodium falciparum malaria in the experimental studies (Nosten et al., 2000:297; WHO, 2010:17). However, the successful formulation of a solid oral dosage form and fixed dosage combination of artesunate and mefloquine remains both a market opportunity and a challenge. Artesunate and mefloquine both exhibited poor flow properties. Furthermore, different elimination half-lives, treatment dosages as well as solubility properties of artesunate and mefloquine required different formulation approaches. To substantiate the FDA’s pharmaceutical quality by design concept, the double fixed-dose combination of artesunate and mefloquine required strict preliminary formulation considerations regarding compatibility between excipients and between the APIs. Materials and process methods were only considered if theoretically and experimentally proved safe. Infrared absorption spectroscopy (IR) and X-ray powder diffraction (XRPD) data proved compatibility between ingredients and stability during the complete manufacturing process by a peak by peak correlation. Scanning Electron Micrographs (SEM) provided explanations for the inferior flow properties exhibited by the investigated APIs. Particle size analysis and SEM micrographs confirmed that the larger, rounder and more consistently sized particles of the granulated APIs contributed to improved flow under the specified testing conditions. A compressible mixture containing 615 mg of the APIs in accordance with the WHO recommendation of 25 mg/kg of mefloquine taken in two or three divided dosages, and 4 mg/kg/day for 3 days of artesunate for uncomplicated falciparum malaria was developed. Mini-tablets of artesunate and mefloquine were compressed separately and successfully with the required therapeutic dosages and complied with pharmacopoeial standards. Preformulation studies eventually led to a formula for a double fixed-dose combination and with the specific aim of delaying the release of artesunate due to its short half-life. A factorial design revealed the predominant factors contributing to the successful wet granulation of artesunate and mefloquine. A fractional factorial design identified the optimum factors and factor levels. The application of the granulation fluid (20% w/w) proved to be sufficient by a spraying method for both artesunate and mefloquine. A compatible acrylic polymer and coating agent for artesunate, Eudragit® L100 was employed to delay the release of approximately half of the artesunate dose from the double fixed-dose combination tablet until a pH of 6.8. A compressible mixture was identified and formulated to contain 200 mg of artesunate and 415 mg of mefloquine per tablet. The physical properties of the tablets complied with BP standards. An HPLC method from available literature was adapted and validated for analytical procedures. Dissolution studies according to a USP method were conducted to verify and quantify the release of the APIs in the double fixed-dose combination. The initial dissolution rate (DRi) of artesunate and mefloquine in the acidic dissolution medium was rapid as required. The enteric coated fraction of the artesunate exhibited no release in an acidic environment after 2 hours, but rapid release in a medium with a pH of 6.8. The structure of the granulated particles of mefloquine may have contributed to its first order release profile in the dissolution mediums. A linear correlation was present between the rate of mefloquine release and the percentage of mefloquine dissolved (R2 = 0.9484). Additionally, a linear relationship was found between the logarithm of the percentage mefloquine remaining against time (R2 = 0.9908). First order drug release is the dominant release profile found in the pharmaceutical industry today and is coherent with the kinetics of release obtained for mefloquine. A concept pre-clinical phase, double fixed-dose combination solid oral dosage form for artesunate and mefloquine was developed. The double fixed-dose combination was designed in accordance with the WHO’s recommendation for an oral dosage regimen of artesunate and mefloquine for the treatment of uncomplicated falciparum malaria. The specifications of the double fixed-dose combination were developed in close accordance with the FDA’s quality by design concept and WHO recommendations. An HPLC analytical procedure was developed to verify the presence of artesunate and mefloquine. The dissolution profiles of artesunate and mefloquine were investigated during the dissolution studies. / PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

Malaria is a life–threatening disease caused by Plasmodium spp and causes over one million deaths annually. The complex life cycle of the malaria parasite offers several points of attack for the antimalarial drugs. The rapid spread of resistance against antimalarial drugs, especially chloroquine and pyrimethamine–sulphadoxine, emphasises the need for new alternatives or modification of existing drugs. Artemisinin–based combination therapies (ACT’s) with different targets prevent or delay the development of drug resistance and therefore have been adopted as first–line therapy by all endemic countries. Proguanil–dapsone, an antifolate combination is more active than pyrimethamine–sulphadoxine and is being considered as an alternative to pyrimethamine–sulphadoxine. Artesunate–proguanil–dapsone is a new ACT that has wellmatched pharmacokinetics and is relatively rapidly eliminated; therefore there is a reduced risk of exposure to any single compound and potentially a decreasing risk of resistance. A few studies have been done on a triple fixed–dose combination therapy for malaria treatment and such a combination for artesunate, proguanil and dapsone are not currently investigated, manufactured or distributed. The aim of this study was to develop a triple fixed–dose combination for artesunate, proguanil and dapsone. The formulation was developed in three phases; basic formulation development, employing factorial design to obtain two possible optimised formulations and evaluating the optimised formulations. During the formulation development the most suitable manufacturing procedure and excipients were selected. A full 24 factorial design (four factors at two levels) was used to obtain the optimised formulations. As end–points to identify the optimised formulations, weight variation, friability, crushing strength and disintegration of the tablets, were used. Statistical analysis (one way ANOVA) was used to identify optimal formulations. To identify any interaction between the active pharmaceutical ingredients (API’s) and the API’s and excipients, differential scanning calorimetry was done. Flow properties of the powder mixtures (of the optimised formulations) were characterised by means of angle of repose; critical orifice diameter (COD); bulk density and tapped density; and flow rate. Tablets of the two optimised powder formulations were compressed. The tablets were evaluated and characterised in terms of weight variation, friability, crushing strength, disintegration and dissolution behaviour. Initial formulation development indicated that wet granulation was the most suitable manufacturing method. The results from the factorial design indicated that different amounts (% w/w) of the lubricant and binder as well as two different fillers influenced the weight variation, crushing strength and disintegration statistically significant. Two formulations containing two different fillers (microcrystalline cellulose or Avicel® PH 101, and lactose or Granulac® 200) were found to be within specifications and ideal for manufacturing. Tablets prepared from the FA formulation (formulation containing Avicel® PH 101) complied with the standards and guidelines for weight variation, friability, crushing strength and disintegration as set by the British Pharmacopoeia (BP). Tablets had an average crushing strength of 121.56 ± 0.022 N. Tablets disintegrated within 52.00 seconds and a maximum weight loss of 0.68% occurred during the friability test. Weight variation of the tablets prepared from the FG formulation (formulation containing Granulac® 200) complied with the standards. Average crushing strength was 91.99 ± 6.008 N and the tablets disintegrated within 140.00 seconds. Percentage friability (1.024%) did not comply with the guideline of a percentage friability of less than 1%, however, no cracked or broken tablets were seen. Dissolution showed that 98, 93 and 94% of artesunate, proguanil and dapsone were respectively released (of the label value) within 15 minutes for the FA formulations. Release of artesunate, proguanil and dapsone for the FG formulation was 62, 85 and 92% for the same time period. The release of the three API’s (the FG formulation) increased to 78, 89 and 92%, respectively, after 45 minutes. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2012.

Malaria is a life–threatening disease caused by Plasmodium spp and causes over one million deaths annually. The complex life cycle of the malaria parasite offers several points of attack for the antimalarial drugs. The rapid spread of resistance against antimalarial drugs, especially chloroquine and pyrimethamine–sulphadoxine, emphasises the need for new alternatives or modification of existing drugs. Artemisinin–based combination therapies (ACT’s) with different targets prevent or delay the development of drug resistance and therefore have been adopted as first–line therapy by all endemic countries. Proguanil–dapsone, an antifolate combination is more active than pyrimethamine–sulphadoxine and is being considered as an alternative to pyrimethamine–sulphadoxine. Artesunate–proguanil–dapsone is a new ACT that has wellmatched pharmacokinetics and is relatively rapidly eliminated; therefore there is a reduced risk of exposure to any single compound and potentially a decreasing risk of resistance. A few studies have been done on a triple fixed–dose combination therapy for malaria treatment and such a combination for artesunate, proguanil and dapsone are not currently investigated, manufactured or distributed. The aim of this study was to develop a triple fixed–dose combination for artesunate, proguanil and dapsone. The formulation was developed in three phases; basic formulation development, employing factorial design to obtain two possible optimised formulations and evaluating the optimised formulations. During the formulation development the most suitable manufacturing procedure and excipients were selected. A full 24 factorial design (four factors at two levels) was used to obtain the optimised formulations. As end–points to identify the optimised formulations, weight variation, friability, crushing strength and disintegration of the tablets, were used. Statistical analysis (one way ANOVA) was used to identify optimal formulations. To identify any interaction between the active pharmaceutical ingredients (API’s) and the API’s and excipients, differential scanning calorimetry was done. Flow properties of the powder mixtures (of the optimised formulations) were characterised by means of angle of repose; critical orifice diameter (COD); bulk density and tapped density; and flow rate. Tablets of the two optimised powder formulations were compressed. The tablets were evaluated and characterised in terms of weight variation, friability, crushing strength, disintegration and dissolution behaviour. Initial formulation development indicated that wet granulation was the most suitable manufacturing method. The results from the factorial design indicated that different amounts (% w/w) of the lubricant and binder as well as two different fillers influenced the weight variation, crushing strength and disintegration statistically significant. Two formulations containing two different fillers (microcrystalline cellulose or Avicel® PH 101, and lactose or Granulac® 200) were found to be within specifications and ideal for manufacturing. Tablets prepared from the FA formulation (formulation containing Avicel® PH 101) complied with the standards and guidelines for weight variation, friability, crushing strength and disintegration as set by the British Pharmacopoeia (BP). Tablets had an average crushing strength of 121.56 ± 0.022 N. Tablets disintegrated within 52.00 seconds and a maximum weight loss of 0.68% occurred during the friability test. Weight variation of the tablets prepared from the FG formulation (formulation containing Granulac® 200) complied with the standards. Average crushing strength was 91.99 ± 6.008 N and the tablets disintegrated within 140.00 seconds. Percentage friability (1.024%) did not comply with the guideline of a percentage friability of less than 1%, however, no cracked or broken tablets were seen. Dissolution showed that 98, 93 and 94% of artesunate, proguanil and dapsone were respectively released (of the label value) within 15 minutes for the FA formulations. Release of artesunate, proguanil and dapsone for the FG formulation was 62, 85 and 92% for the same time period. The release of the three API’s (the FG formulation) increased to 78, 89 and 92%, respectively, after 45 minutes. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2012.

As folhas de Maytenus ilicifolia são amplamente utilizadas na medicina tradicional brasileira no tratamento de distúrbios gástricos. Após a comprovação de sua eficácia e segurança, a referida droga vegetal tem sido objeto de diversos estudos com a finalidade de estabelecer parâmetros para o controle de qualidade. Neste sentido, foi avaliada a viabilidade do desenvolvimento de um método analítico fundamentado na precipitação de taninos empregando povidona como agente seqüestrante. Os dados revelaram que a remoção de taninos em solução é satisfatória quando empregada a povidona insolúvel. Foi observado que o polímero também é capaz de precipitar outros polifenóis além dos taninos presentes na solução extrativa de M. ilicifolia. Entretanto, as interações do polímero ocorrem preferencialmente com os derivados catéquicos. Adicionalmente foi desenvolvido e validado um método por CLAE para separação e quantificação de catequina e epicatequina em produtos derivados de M. ilicifolia. Não foram detectadas variações nas áreas dos picos ou nos tempos de retenção durante os ensaios de avaliação do método, sugerindo que as condições cromatográficas empregadas são satisfatórias. Para viabilizar a preparação de produto seco por aspersäo (PSA) em torre de secagem piloto munida de aspersor rotatório, foi necessária a concentração da solução extrativa. A operação foi realizada sob pressão reduzida até alcangar um teor de sólidos mínimo de 15 % (m/m). A operação de secagem da solução concentrada apresentou rendimento de 90 % e o PSA obtido apresentou partículas esféricas, com superfície rugosa e tamanho médio de 22,5 um. A caracterização tecnológica do material revelou que as suas propriedades tecnológicas, tais como, densidades, compressibilidade e fluxo, foram incrementadas quando comparados com o produto preparado em equipamento de bancada. Entretanto, estas modificações não foram suficientes para viabilizar sua compressão direta. Assim sendo, o material foi compactado em máquina de comprimir e em rolos para produção de grânulos. A análise do perfil compressional do PSA e dos granulados, empregando o modelo de Heckel, revelou que o aumento da força de compactação durante a operação de granulação foi o principal responsável pela diminuição no potencial de deformação plástica dos grânulos. Como conseqüência, a recompressão dos grânulos em máquina de comprimir originou compactos com dureza inferior àqueles preparados diretamente do complexo farmacêutico. Enquanto o PSA apresentou reduzida tendência ao rearranjo particular nos estágios iniciais da compressão, os grânulos sofreram intensa reacomodação decorrente da fragmentação e formação de novas pontes, assumindo comportamento plástico em pressões de compressão mais elevadas. Por fim, comprimidos contendo teor elevado de granulado de PSA foram preparados utilizando como adjuvantes a celulose microcristalina, o dióxido de silício coloidal e a croscarmelose sódica. A influência da concentração de dióxido de silício coloidal e croscarmelose sódica na formulação, sobre as respostas de dureza, friabilidade e tempo de desintegração dos comprimidos foram avaliadas através de um Desenho Composto Central. Os dados experimentais foram analisados estatisticamente, utilizando os modelos matemáticos para gerar superfícies de resposta. Os resultados indicaram que a concentração de dióxido de silício coloidal foi inversamente relacionada às respostas de dureza e friabilidade, enquanto que a concentração de croscarmelose sódica foi a principal responsável pela redução no tempo de desintegração. As condições ótimas foram selecionadas através da sobreposição dos gráficos, buscando uma formulação com menor tempo de desintegração, menor friabilidade e o máximo de dureza. A formulação eleita deve conter 1,2 % (m/m) de dióxido de silício coloidal e 5,0 % (m/m) de croscarmelose sódica. Nestas condições os comprimidos apresentaram dureza de 107,9 N, friabilidade de 0,56 % (m/m) e desintegração máxima em 6,8 min. / The leaves of Maytenus ilicifolia are widely used within the traditional Brazilian medicine due to its properties against gastric disorders. Once proved its efficacy and safety, this vegetable drug has been the object of several studies to establish the basis for quality control. Taking this into consideration, it was necessary to evaluate the feasibility of developing an analytical method based on the precipitation of tannins, by using polyvinylpyrrolidone for precipitation. The data have shown that the removal of the tannins in solution was successful when insoluble polyvinylpyrrolidone was used. Hereby it was observed that the polymer has also the ability to precipitate other polyphenols besides the tannins from the aqueous solution of M. ilicifolia. However, the interactions of the polymer happened mostly with the condensed tannins. Further it was developed and also validated an HPLC method to separate and quantify catechin and epicatechin present in aqueous extracts of M. ilicifolia. No significant variations of peak areas or retention times were observed when the evaluation of the method was executed, showing satisfactory chromatographic conditions. In order to make a spray dried extract (SDE) using a spray-drier fitted out with a rotary atomizer, it was necessary to concentrate the extractive solution. This operation had been performed under reduced pressure until a content of 15 % solids was achieved. The drying of the concentrated solution lead to a yield of 90 %, and the obtained SDE presented spherical particles, which have a rough surface and a mean particle size of 22,51.1.m. The technological characterization of the SDE showed that attributes such as densities (tap and bulk), compressibility and flow, have been improved when compared to the product prepared using a mini spray-drier supplied with a pneumatic nozzle. However, these modifications were not enough to enable its direct compression. Therefore, the material was compacted to produce granules after slugging or roller compaction, The compressional analysis of the SDE and each granule batch using the Heckel equation proved that the increase in the compaction force once processing the granulation was the main factor to reduce the material's ability to undergo plastic deformation. Consequently, the recompression of the granules in a tablet press led to compacts with a lower crushing strength compared to that prepared by direct compression of the pharmaceutical complex. Whereas the SDE has shown a reduced tendency to particle rearrangement at early stage of compression, the granules showed an intense fragmentation and rebound behavior, presenting a plastic behavior when higher compaction pressures were used. Finally, tablets containing a high dose of granulated spray dried extract of M. ilicifolia were prepared by using the following excipients: microcrystalline cellulose (filler/binder), colloidal silicon dioxide (glidant and moisture adsorber) and cross-linked carboxymethylcellulose (disintegrant). The influences of colloidal silicon dioxide (CSD) and cross-linked carboxymethylcellulose (CMC-Na) on the tablet hardness, disintegration time and friability were evaluated by a central composite design. The data were analyzed statistically and mathematical models were used to create response surfaces. The results have indicated that the concentration of CSD shows an inverse relation to the responses of hardness and friability, while the concentration of CMC-Na was the most important factor that caused a reduction of the time necessary for total disintegration. The optimal conditions for processing were chosen by the overlapping of graphics, taking into consideration that the formulation should present a minimum of disintegration time, lower friability and a maximum of hardness. Thus, it was found that the best formulation should have a content of 1.2% (w/w) of CSD and 5.0% (w/w) of CMC-Na. Regarding these conditions, the tablets have shown a hardness of 107.9 N, friability of 0.56% (w/w) and a disintegration time of 6.8 min.

As folhas de Maytenus ilicifolia são amplamente utilizadas na medicina tradicional brasileira no tratamento de distúrbios gástricos. Após a comprovação de sua eficácia e segurança, a referida droga vegetal tem sido objeto de diversos estudos com a finalidade de estabelecer parâmetros para o controle de qualidade. Neste sentido, foi avaliada a viabilidade do desenvolvimento de um método analítico fundamentado na precipitação de taninos empregando povidona como agente seqüestrante. Os dados revelaram que a remoção de taninos em solução é satisfatória quando empregada a povidona insolúvel. Foi observado que o polímero também é capaz de precipitar outros polifenóis além dos taninos presentes na solução extrativa de M. ilicifolia. Entretanto, as interações do polímero ocorrem preferencialmente com os derivados catéquicos. Adicionalmente foi desenvolvido e validado um método por CLAE para separação e quantificação de catequina e epicatequina em produtos derivados de M. ilicifolia. Não foram detectadas variações nas áreas dos picos ou nos tempos de retenção durante os ensaios de avaliação do método, sugerindo que as condições cromatográficas empregadas são satisfatórias. Para viabilizar a preparação de produto seco por aspersäo (PSA) em torre de secagem piloto munida de aspersor rotatório, foi necessária a concentração da solução extrativa. A operação foi realizada sob pressão reduzida até alcangar um teor de sólidos mínimo de 15 % (m/m). A operação de secagem da solução concentrada apresentou rendimento de 90 % e o PSA obtido apresentou partículas esféricas, com superfície rugosa e tamanho médio de 22,5 um. A caracterização tecnológica do material revelou que as suas propriedades tecnológicas, tais como, densidades, compressibilidade e fluxo, foram incrementadas quando comparados com o produto preparado em equipamento de bancada. Entretanto, estas modificações não foram suficientes para viabilizar sua compressão direta. Assim sendo, o material foi compactado em máquina de comprimir e em rolos para produção de grânulos. A análise do perfil compressional do PSA e dos granulados, empregando o modelo de Heckel, revelou que o aumento da força de compactação durante a operação de granulação foi o principal responsável pela diminuição no potencial de deformação plástica dos grânulos. Como conseqüência, a recompressão dos grânulos em máquina de comprimir originou compactos com dureza inferior àqueles preparados diretamente do complexo farmacêutico. Enquanto o PSA apresentou reduzida tendência ao rearranjo particular nos estágios iniciais da compressão, os grânulos sofreram intensa reacomodação decorrente da fragmentação e formação de novas pontes, assumindo comportamento plástico em pressões de compressão mais elevadas. Por fim, comprimidos contendo teor elevado de granulado de PSA foram preparados utilizando como adjuvantes a celulose microcristalina, o dióxido de silício coloidal e a croscarmelose sódica. A influência da concentração de dióxido de silício coloidal e croscarmelose sódica na formulação, sobre as respostas de dureza, friabilidade e tempo de desintegração dos comprimidos foram avaliadas através de um Desenho Composto Central. Os dados experimentais foram analisados estatisticamente, utilizando os modelos matemáticos para gerar superfícies de resposta. Os resultados indicaram que a concentração de dióxido de silício coloidal foi inversamente relacionada às respostas de dureza e friabilidade, enquanto que a concentração de croscarmelose sódica foi a principal responsável pela redução no tempo de desintegração. As condições ótimas foram selecionadas através da sobreposição dos gráficos, buscando uma formulação com menor tempo de desintegração, menor friabilidade e o máximo de dureza. A formulação eleita deve conter 1,2 % (m/m) de dióxido de silício coloidal e 5,0 % (m/m) de croscarmelose sódica. Nestas condições os comprimidos apresentaram dureza de 107,9 N, friabilidade de 0,56 % (m/m) e desintegração máxima em 6,8 min. / The leaves of Maytenus ilicifolia are widely used within the traditional Brazilian medicine due to its properties against gastric disorders. Once proved its efficacy and safety, this vegetable drug has been the object of several studies to establish the basis for quality control. Taking this into consideration, it was necessary to evaluate the feasibility of developing an analytical method based on the precipitation of tannins, by using polyvinylpyrrolidone for precipitation. The data have shown that the removal of the tannins in solution was successful when insoluble polyvinylpyrrolidone was used. Hereby it was observed that the polymer has also the ability to precipitate other polyphenols besides the tannins from the aqueous solution of M. ilicifolia. However, the interactions of the polymer happened mostly with the condensed tannins. Further it was developed and also validated an HPLC method to separate and quantify catechin and epicatechin present in aqueous extracts of M. ilicifolia. No significant variations of peak areas or retention times were observed when the evaluation of the method was executed, showing satisfactory chromatographic conditions. In order to make a spray dried extract (SDE) using a spray-drier fitted out with a rotary atomizer, it was necessary to concentrate the extractive solution. This operation had been performed under reduced pressure until a content of 15 % solids was achieved. The drying of the concentrated solution lead to a yield of 90 %, and the obtained SDE presented spherical particles, which have a rough surface and a mean particle size of 22,51.1.m. The technological characterization of the SDE showed that attributes such as densities (tap and bulk), compressibility and flow, have been improved when compared to the product prepared using a mini spray-drier supplied with a pneumatic nozzle. However, these modifications were not enough to enable its direct compression. Therefore, the material was compacted to produce granules after slugging or roller compaction, The compressional analysis of the SDE and each granule batch using the Heckel equation proved that the increase in the compaction force once processing the granulation was the main factor to reduce the material's ability to undergo plastic deformation. Consequently, the recompression of the granules in a tablet press led to compacts with a lower crushing strength compared to that prepared by direct compression of the pharmaceutical complex. Whereas the SDE has shown a reduced tendency to particle rearrangement at early stage of compression, the granules showed an intense fragmentation and rebound behavior, presenting a plastic behavior when higher compaction pressures were used. Finally, tablets containing a high dose of granulated spray dried extract of M. ilicifolia were prepared by using the following excipients: microcrystalline cellulose (filler/binder), colloidal silicon dioxide (glidant and moisture adsorber) and cross-linked carboxymethylcellulose (disintegrant). The influences of colloidal silicon dioxide (CSD) and cross-linked carboxymethylcellulose (CMC-Na) on the tablet hardness, disintegration time and friability were evaluated by a central composite design. The data were analyzed statistically and mathematical models were used to create response surfaces. The results have indicated that the concentration of CSD shows an inverse relation to the responses of hardness and friability, while the concentration of CMC-Na was the most important factor that caused a reduction of the time necessary for total disintegration. The optimal conditions for processing were chosen by the overlapping of graphics, taking into consideration that the formulation should present a minimum of disintegration time, lower friability and a maximum of hardness. Thus, it was found that the best formulation should have a content of 1.2% (w/w) of CSD and 5.0% (w/w) of CMC-Na. Regarding these conditions, the tablets have shown a hardness of 107.9 N, friability of 0.56% (w/w) and a disintegration time of 6.8 min.

Abstract The main aim of the European Union’s waste legislation and the corresponding Finnish waste legislation is to reduce the production of waste. Further, the aims of the European Union’s growth strategy are to reduce the production of greenhouse gases, increase the use of renewable energy, and improve energy efficiency. According to the renewed Waste Tax Act, a waste tax has to be paid on all fly ashes that are deposited in landfills in Finland. A large amount of wood- and peat-based fly ashes are formed annually in Finland, and the amount is likely to increase in the future due to the increasing use of renewable energy. Previously, these ashes have mainly been deposited in industrial landfills, but the need to utilize the fly ashes has increased recently due to changes in waste legislation. In this thesis, several issues related to the utilization of wood- and peat-based fly ash were studied, with the general objective of improving the utilization potential of such ashes. As the first stage of this research, the suitability of willow ash for use as a fertilizer was studied. Willow ash would be well suited for use as a fertilizer due to its very high nutrient content. However, cadmium, a heavy metal, was found to be enriched in the ashes of the studied willow species. Due to this, special attention should be paid when choosing willow species for energy production. In the second stage of the research, the possibility of improving the strength development of wood- and peat-based fly ashes, as well as the possibility of stabilizing fly ash containing high amounts of heavy metals via the addition of cement and/or alkali activation, was investigated. Strength development was found to be dependent on the amount of reactive calcium and the ratio between that amount of reactive calcium and the sum of the reactive silicon, aluminum, and sulfur (Ca/(Si + Al + S)). The studied methods performed well in terms of stabilizing barium, copper, lead, and zinc. During the next stage, the effect of different chemical digestion methods, which are regulated by the Finnish waste legislation, on the utilization potential of fly ash was studied. The digestion method had a significant impact on the results of the potassium content analysis, which could affect the possibility of using fly ash as a fertilizer. As the final stage of the research, the co-granulation of ash with sewage sludge and lime was studied. From a technical point of view, the co-granulation was successful, although the compressive strength of the granules was low. Additionally, an insufficient nitrogen content was achieved with a sludge addition of 20-40 weight%. / Tiivistelmä Euroopan unionin jätelainsäädännön ja sitä vastaavan suomalaisen lainsäädännön tavoitteena on ehkäistä jätteiden muodostumista. Euroopan Unionin kasvustrategian tavoitteena on vähentää kasvihuonekaasupäästöjä, lisätä uusiutuvan energian käyttöä ja parantaa energiatehokkuutta. Uudistetun jäteverolain mukaan kaikista kaato-paikoille sijoitetuista lentotuhkista tulee Suomessa maksaa jäteveroa. Suomessa puu- ja turveperäisiä lentotuhkia muodostuu vuosittain suuria määriä ja määrä tulee vielä kasvamaan uusiutuvan energiankäytön lisääntyessä. Aiemmin nämä tuhkat ovat päätyneet pääasiassa läjitykseen teollisuuden kaatopaikoille, mutta muuttuneen jätelainsäädännön seurauksena tarve hyödyntää lentotuhkia on lisääntynyt. Tässä väitöstyössä tutkittiin puu- ja turveperäisten tuhkien hyödyntämiseen liittyviä kysymyksiä. Työn yleistavoitteena oli parantaa tuhkien hyödyntämis-mahdollisuuksia. Tutkimuksen ensimmäisessä vaiheessa tutkittiin pajutuhkan soveltuvuutta lannoitteeksi. Pajutuhka soveltuisi hyvin lannoitteeksi erittäin hyvien ravinne-pitoisuuksien ansiosta. Raskasmetalleista kadmiumin havaittiin kuitenkin rikastuvan tutkittujen pajulajien tuhkiin. Tähän tulisi kiinnittää erityishuomiota, kun pajulajeja valitaan energiantuotantoa varten. Tutkimuksen toisessa vaiheessa selvitettiin mahdollisuutta parantaa turpeen ja puun lentotuhkien lujittumista sekä raskasmetallipitoisen lentotuhkan stabiloimista sementtilisäyksen ja/tai alkaliaktivoinnin avulla. Lujuuden kehitys riippui reaktiivisen kalsiumin määrästä sekä reaktiivisen kalsiumin määrän ja reaktiivisten piin, alumiinin ja rikin määrien summan välisestä suhteesta (Ca/(Si + Al + S)). Tutkitut menetelmät toimivat hyvin bariumin, kuparin, lyijyn ja sinkin stabiloinnissa. Seuraavassa vaiheessa selvitettiin Suomen lainsäädännössä määritettyjen kemiallisten hajotusmenetelmien vaikutusta tuhkan hyödyntämispotentiaaliin. Hajotusmenetelmällä oli suuri merkitys kaliumin pitoisuutta määritettäessä, mikä voi vaikuttaa lentotuhkan hyödynnettävyyteen lannoitteena. Viimeisessä vaiheessa tutkittiin tuhkan yhteisrakeistusta lietteen ja kalkin kanssa. Teknisesti yhteisrakeistus onnistui hyvin, mutta rakeiden puristuslujuus oli alhainen. Lisäksi 20 - 40 paino% lietelisäyksellä ei rakeisiin saatu riittävän korkeaa typpipitoisuutta.

<p>Predmet&nbsp; istraživanja ove&nbsp; doktorske&nbsp; disertacije&nbsp; su srednje&nbsp; i&nbsp; gornje&nbsp; pleistocene&nbsp; lesno-paleozemlji&scaron;ne sekvence&nbsp; (LPS)&nbsp; u&nbsp; dolini&nbsp; Južne Morave&nbsp; na&nbsp; profilima&nbsp; ciglana&nbsp; u&nbsp; Stalaću i Belotincu.&nbsp; Ove&nbsp; LPC&nbsp; predstavljaju jedinstven&nbsp; kontinentalni&nbsp; arhiv&nbsp; paleoklimatskih&nbsp; i paleoekolo&scaron;kih promena&nbsp; tokom&nbsp; pleistocena&nbsp; u&nbsp; ovom&nbsp; delu&nbsp; Balkanskog&nbsp; poluostrva.&nbsp; Nakon detalʁnihterenskih istraživanjai uzorkovanja na pomenutim lesnim profilima, razmatrano je vi&scaron;e istraživačkihproblema.&nbsp; Izvr&scaron;eno&nbsp; jepedo- i lito-stratigrafsko opisivanje&nbsp; naoba profila.&nbsp; Na njima je&nbsp; zapaženo nekoliko&nbsp; metara&nbsp; moćnih glacijalnih&nbsp; lesnih&nbsp; horizonata&nbsp; i nekoliko&nbsp; interglacijalnih<br />pedokomleksa,&nbsp; koji&nbsp; se vizuelno&nbsp; jasno&nbsp; razlikuju.&nbsp; Izvr&scaron;ena&nbsp; je rekonstrukcija&nbsp; relʁefa na&nbsp; osnovu prostornih odnosa LPS. Ukupna deblʁinaanalizirananih LPS iznosi:&nbsp; u&nbsp; Stalaću&nbsp; približno20,5 m, gde&nbsp; je&nbsp; zapaženo po&nbsp; sedam&nbsp; pedokompleksa&nbsp; i&nbsp; lesnih&nbsp; horizonata,&nbsp; dok&nbsp; je&nbsp; deblʁina u&nbsp; Belotincu analiziranih LPS 8 m. Vrednosti magnetnog susceptibiliteta (MS)&nbsp; u&nbsp; Stalaćuukazuje da poreklo pra&scaron;kastog fluvijalnog materijala&nbsp; potiče&nbsp; izdva nezavisna izvora.&nbsp; Veće vrednosti&nbsp; MS prisutne&nbsp; su u materijalu koji&nbsp; potiče&nbsp; iz sliva Zapadne Morave. Dok manje vrednosti ukazuju da&nbsp; je poreklo materijala iz JužneMorave. U Belotincu manje vrednosti MS ukazuju da je poreklo materijala iz<br />sliva&nbsp; Južne Morave.&nbsp; Tumačenjem rezultata apsolutnog luminescentnog datiranja&nbsp; na oba profila ukazuju da&nbsp; su LPS nastajale tokom poslednjih ~ 350.000 godina u&nbsp; Stalaću i ~ 35.500 godina u Belotincu. Granulometrijski sastav LPS u Stalaću&nbsp; je&nbsp; sačinjen od pet različitih frakcija&nbsp; &lt; 2,0 &mu;m, 2,0-6,2&nbsp; &mu;m,&nbsp; 6,2-20,0&nbsp; &mu;m,&nbsp; 20,0-63,0&nbsp; &mu;mi&nbsp; &gt;63,0&nbsp; &mu;m.&nbsp; Dok,&nbsp; su u&nbsp; Belotincu&nbsp; najvi&scaron;e&nbsp; zastupljene krupne&nbsp; čestice od&nbsp; 51&nbsp; %&nbsp; do&nbsp; 66&nbsp; %&nbsp; i&nbsp; grube&nbsp; frakcije,&nbsp; koje&nbsp; ukazuju&nbsp; na&nbsp; neposrednu&nbsp; blizinu&nbsp; izvora porekla&nbsp; materijala.&nbsp; Boja&nbsp; LPS&nbsp; na&nbsp; profilima&nbsp; u&nbsp; Stalaću i&nbsp; Belotincu&nbsp; menja&nbsp; se i&nbsp; kovarira&nbsp; sa&nbsp; MS. Kolorimetrijski rezultati ukazuju, slično MS rezultatima, da lesni sedimenti potiču jednim delom iz&nbsp; Južne Morave,&nbsp; a&nbsp; drugim&nbsp; delom&nbsp; iz Zapadne&nbsp; Morave.&nbsp; Geohemijske&nbsp; analize&nbsp; ukazuju&nbsp; na dominantno&nbsp; silikatno&nbsp; raspadanje&nbsp; čestica,&nbsp; slično dunavskom&nbsp; lesu.&nbsp; Geohemijski&nbsp; sastav&nbsp; LPS Belotinc&nbsp; pokazuje&nbsp; da&nbsp; pedokompleks&nbsp; je&nbsp; obogaćen organskog&nbsp; ugljenika,&nbsp; dok&nbsp; su u&nbsp; lesnim slojevima&nbsp; primećene&nbsp; niže vrednosti&nbsp; organskog&nbsp; ugljenika.&nbsp; Generalno&nbsp; tumačenje svih&nbsp; rezultata ukazuje na dominantan mediteranski klimatski uticaj na LPS u srednjem pleistocenu, dok&nbsp; je u gornjem i mlađem pleistocenu bio dominantan uticaj kontinentalne klime.</p> / <p>The&nbsp; research&nbsp; subject&nbsp; of&nbsp; this&nbsp; dissertation&nbsp; are&nbsp; Middle&nbsp; and&nbsp; Upper&nbsp; Pleistocene&nbsp; loesspaleosol&nbsp; sequences&nbsp; (LPS)&nbsp; in&nbsp; the&nbsp; South&nbsp; Morava&nbsp; valley,&nbsp; at&nbsp; brickyards&rsquo; profiles&nbsp; in&nbsp; Stalac&nbsp; and Belotinac. These LPS represent a unique continental record of paleoclimate and paleoecological changes during Pleistocene in this part of the Balkan Peninsula. After detailed terrain researches and&nbsp; samplings&nbsp; at&nbsp; the&nbsp; two&nbsp; loess&nbsp; profiles,&nbsp; several&nbsp; research&nbsp; problems&nbsp; were&nbsp; discussed.&nbsp; Pedostratigraphic and litho-stratigraphic descriptions were done for both profiles. There were found several&nbsp; meters&nbsp; of&nbsp; powerful&nbsp; glacial&nbsp; loess&nbsp; horizons&nbsp; and&nbsp; several&nbsp; interglacial&nbsp; pedocomplexes&nbsp; that were visually distinctive. A relief reconstruction was carried out based on spatial LPS ratios. The total&nbsp; thickness&nbsp; of&nbsp; the&nbsp; analyzed&nbsp; LPS&nbsp; is:&nbsp; approximately&nbsp; 20.5&nbsp; m&nbsp; in&nbsp; Stalac,&nbsp; where&nbsp; seven pedocomplexes&nbsp; and&nbsp; seven&nbsp; horizons&nbsp; were&nbsp; observed,&nbsp; whereas&nbsp; thickness&nbsp; of&nbsp; analyzed&nbsp; LPS&nbsp; in Belotinac was 8 &nbsp; m. The magnetic susceptibility (MS) values in Stalacpoint at two independent sources of dusty fluvial materials. The higher MS values are observed in materials originating from the West Morava basin, while lower MS values indicate that materials originate from the South&nbsp; Morava&nbsp; basin.&nbsp; Interpretations&nbsp; of&nbsp; absolute&nbsp; luminescent&nbsp; dating&nbsp; results&nbsp; at&nbsp; both&nbsp; profiles indicate&nbsp; that&nbsp; the&nbsp; LPS&nbsp; were&nbsp; formed&nbsp; during&nbsp; last&nbsp; ~&nbsp; 350.000&nbsp; years&nbsp; in&nbsp; Stalac&nbsp; and&nbsp; ~&nbsp; 35.500&nbsp; in Belotinac. The LPS in Stalac is granulometrically consisted of five different fractions: &lt; 2.0 &mu;m, 2.0-6.2 &mu;m, 6.2-20.0&nbsp; &mu;m, 20.0-63.0&nbsp; &mu;mand &gt;63.0&nbsp; &mu;m. In Belotinac the most frequent particles are&nbsp; the&nbsp; large&nbsp; ones&nbsp; varying&nbsp; from&nbsp; 51%&nbsp; to&nbsp; 66%&nbsp; and&nbsp; rough&nbsp; fractions,&nbsp; which&nbsp; indicates&nbsp; that&nbsp; the material source was in its immediate proximity. The LPS colours both in Stalac and Belotinac covariate with the MS. Similarly to the MS results, the colorimetric results indicate that a part of the loess sediments originates from the South Morava, and the other part from the West Morava. Geochemical analyses point at a dominant silicate particle decomposition, which is similar to the Danube&nbsp; loess.&nbsp; Geochemical&nbsp; composition&nbsp; of&nbsp; BelotinacLPS&nbsp; shows&nbsp; an&nbsp; organic-carbon-enriched pedocomplex,&nbsp; while&nbsp; lower&nbsp; values&nbsp; of&nbsp; the&nbsp; organic&nbsp; carbon&nbsp; are&nbsp; observed&nbsp; in&nbsp; the&nbsp; loess&nbsp; layers.&nbsp; The general interpretation of the results points at dominant Mediterranean climate influence on the LPS&nbsp; in&nbsp; the&nbsp; Middle&nbsp; Pleistocene,&nbsp; while&nbsp; in&nbsp; the&nbsp; Upper&nbsp; and&nbsp; Younger&nbsp; Pleistocene&nbsp; a&nbsp; continental climate influence was dominant.</p>

Les phénomènes éruptifs du Soleil sont souvent accompagnés par l'accélération de particules chargées qui peuvent avoir des impacts significatifs sur la Terre. Toutefois, le mécanisme responsable de ces phénomènes n'est pas suffisamment bien compris pour qu’on puisse en prédire l'occurence. Les satellites et les observatoires terrestres sondent la photosphère, la chromosphère et la couronne du Soleil et sont essentiels pour l'étude de l'activité solaire. Les simulations numériques tentent de faire le pont entre la physique décrivant l'intérieur de l'étoile et de telles observations. La prochaine étape pour des simulations réalistes serait la prévision à court terme des structures à la surface du Soleil. Les travaux présentés dans cette thèse explorent comment des notions empruntées de la météorologie (e.g., l'assimilation des données) et de l'intelligence artificielle (e.g., les réseaux de neurones) pourraient être utilisées pour la prédiction à court terme de l'activité solaire dans le contexte de la météorologie spatiale. En particulier, nous présentons notre implémentation de l'assimilation des données dans un modèle magnétohydrodynamique (MHD) radiatif du Soleil calme (i.e., en l'absence d'activité magnétique) afin de prédire l'évolution de la granulation solaire durant une courte période de temps. Toutefois, ce ne sont pas toutes les variables du modèle qui peuvent être observées ou mesurées à l'aide d'instruments. Par exemple, les mesures directes des mouvements du plasma à la surface du Soleil sont limitées à la composante le long de la ligne de visée. Plusieurs algorithmes ont donc été développés afin de reconstruire la composante transverse à partir de mesures de l'intensité de la lumière ou du champ magnétique. Nous comparons les champs de vitesse inférés par différentes méthodes, dont un réseau de neurones, afin d'identifier la méthode la mieux adaptée pour générer des observations synthétiques dans une chaîne de réduction des données qui pourraient ensuite être introduites dans notre système pour l'assimilation des données. / Eruptive events of the Sun, which often occur in the context of flares, convert large amounts of magnetic energy into emission and particle acceleration that can have significant impacts on Earth's environment. However, the mechanism responsible for such phenomena is not sufficiently well understood to be able to predict their occurrence. Satellites and ground-based observatories probe the Sun's photosphere, chromosphere and corona and are key in studying solar activity. Numerical models have attempted to bridge the gap between the physics of the solar interior and such observations. The next step for realistic simulations would be to forecast the short term evolution of the Sun's photosphere. The following work explores how notions borrowed from meteorology (e.g., data assimilation) and artificial intelligence (e.g., neural networks) could be used to forecast short term solar activity for space-weather modelling purposes. More specifically, we present an implementation of data assimilation in a radiative MHD model of the Quiet Sun (i.e., in the absence of significant magnetic activity) to forecast its evolution over a short period of time. However, not all model variables are directly observable. For example, direct measurements of plasma motions at the photosphere are limited to the line-of-sight component. Multiple algorithms were consequently developed to reconstruct the transverse component from observed continuum images or magnetograms. We compare velocity fields inferred by different methods, including a neural network, to identify the method best suited to generate instantaneous synthetic observations in a data reduction pipeline that would included in our data assimilation framework.