A pharmaceutical dosage form is an entity that is administered to patients so that they receive an effective dose of an active pharmaceutical ingredient (API). The proper design and formulation of a transdermal dosage form require a thorough understanding of the physiological factors affecting percutaneous penetration and physicochemical characteristics of the API, as well as that of the pharmaceutical exipients that are used during formulation. The API and pharmaceutical excipients must be compatible with one another to produce a formulation that is stable, efficacious, attractive, easy to administer, and safe (Mahato, 2007:11). Amongst others, the physicochemical properties indicate the suitability of the type of dosage form, as well as any potential problems associated with instability, poor permeation and the target site to be reached (Wells & Aulton, 2002:337). Therefore, when developing new or improved dosage forms, it is of utmost importance to evaluate the factors influencing design and formulation to provide the best possible dosage form and formulation for the API in question. Delivery of an API through the skin has long been a promising concept due to its large surface area, ease of access, vast exposure to the circulatory and lymphatic networks, and non-invasive nature of the therapy. This is true whether a local or systemic pharmacological effect is desired (Aukunuru et al., 2007:856). However, most APIs are administered orally as this route is considered to be the simplest, most convenient and safest route of API administration. Since ibuprofen is highly metabolised in the liver and gastrointestinal tract, oral administration thereof results in decreased bioavailability. Furthermore, it also causes gastric mucosal damage, bleeding and ulceration. Another obstacle associated with oral API delivery is that some APIs require continuous delivery which is difficult to achieve (Bouwstra et al., 2003:3). Therefore, there is significant interest to develop topical dosage forms for ibuprofen to avoid side effects associated with oral delivery and to provide relatively consistent API levels at the application site for prolonged periods (Rhee et al., 2003:14). The aim of this study was to determine the influence of selected formulation factors on the transdermal delivery of ibuprofen. In order to achieve this aim, the physicochemical properties of ibuprofen had to be evaluated. The aqueous solubility, pH-solubility profile, octanol-water partition coefficient (log P-value) and octanol-buffer distribution coefficient (log D-values, pH 5 and 7.4) of ibuprofen were determined. According to Naik et al., (2000:319) the ideal aqueous solubility of APIs for transdermal delivery should be more than 1 mg.ml-1. However, results showed that ibuprofen depicted an aqueous solubility of 0.096 mg.ml-1 ± 25.483, which indicated poor water solubility and would therefore be rendered less favourable for transdermal delivery if only considering the aqueous solubility. The pH-solubility profile depicted that ibuprofen was less soluble at low pH-values and more soluble at higher pH-values. Previous research indicated that the ideal log Pvalues for transdermal API permeation of non steroid anti-inflammatory drugs (NSAIDs) are between 2 and 3 (Swart et al., 2005:72). Results obtained during this study indicated a log P-value of 4.238 for ibuprofen. This value was not included in the ideal range, which is an indication that the lipophilic/hydrophilic properties are not ideal, and this might therefore; contribute to poor ibuprofen penetration through the skin. Furthermore, the obtained log D-values at pH 5 and 7.4 were 3.105 and 0.386, respectively. Therefore, it would be expected that ibuprofen incorporated into a formulation prepared at a pH of 5 would more readily permeate the skin compared to ibuprofen incorporated into a formulation prepared at a pH of 7.4. A gel, an emulgel and a Pheroid™ emulgel were formulated at pH 5 and 7.4, in order to examine which dosage form formulated at which pH would deliver enhanced transdermal delivery. Obtained diffusion results of the different semi-solid formulations were furthermore compared to a South African marketed commercial product (Nurofen® gel) in order to establish if a comparable formulation could be obtained. An artificial membrane was used to conduct the membrane permeation studies over a period of 6 h, in order to determine whether ibuprofen was in fact released from the formulations through the membrane. Skin permeation studies were conducted using Franz diffusion cells over a period of 12 h where samples were withdrawn at specified time intervals. All the formulations exhibited an increase in the average cumulative amount of ibuprofen released from the formulations and that permeated the membrane when compared to Nurofen® gel. This increase was statistically significant (p<0.05) for the gel, emulgel and Pheroid™ emulgel at pH 7.4. The gel at pH 7.4 exhibited the highest cumulative amount of ibuprofen that permeated the membrane. Preparations formulated at a pH of 5, did not differ significantly from Nurofen® when the average cumulative amount of ibuprofen that permeated the membrane were compared. The following rank order for the average cumulative amount released from the formulations could be established: Gel (pH 7.4) >>>> Pheroid™ emulgel (pH 7.4) > Emulgel (pH 7.4) >>> Gel (pH 5)> Pheroid™ emulgel (pH 5) ≈ Emulgel (pH 5) > Nurofen® gel. On the other hand, all the formulations exhibited an increase in the average cumulative amount of ibuprofen that permeated the skin when compared to Nurofen® gel. This increase was statistically significant (p < 0.05) for the gel, emulgel and Pheroid™ emulgel at pH 5, as well as the emulgel and Pheroid™ emulgel at pH 7.4. The emulgel at pH 5 exhibited the highest cumulative amount of ibuprofen that permeated the skin. The following rank order for the average cumulative amount released from the formulations and that permeated the skin could be established: Emulgel (pH 5) >> Pheroid™ emulgel (pH 5) > Gel (pH 5) > Emulgel (pH 7.4)> Pheroid™ emulgel (pH 7.4) ≈ Emulgel (pH 7.4) >> Nurofen® gel > Gel (pH 7.4). From this rank order it was clear that a trend was followed where the pH of formulation also played a role in ibuprofen permeation. All the formulations exhibited a higher release rate and flux when compared to Nurofen® gel. This was statistically significant for the emulgel, gel and Pheroid™ emulgel at pH 7.4. The gel at pH 7.4 exhibited the highest release rate and flux. This was observed for the membrane and skin permeation studies. All the formulations (including Nurofen® gel) presented a correlation coefficient (r2) of 0.972 – 0.995 for membrane permeation studies, and 0.950 – 0.978 for skin permeation studies; indicating that the release of ibuprofen from each of the formulations could be described by the Higuchi model. Furthermore, all the formulations exhibited a prolonged lag time compared to Nurofen® gel which indicated that the ibuprofen was retained for a longer time by the base. This was statistically significant (p < 0.05) for the emulgel at pH 7.4, the gel and Pheroid™ emulgel at pH 5. The gel at pH 7.4 exhibited a lag time closest to that of Nurofen® gel and this difference could not be classified as statistically significant (p > 0.286). This was observed for the membrane and skin permeation studies. Nurofen® gel exhibited the highest ibuprofen concentration in the stratum corneum as well as in the epidermis followed by the gel at pH 7.4. However, results obtained for all the formulations indicated that topical as well as transdermal delivery of ibuprofen was achieved. The pH of a formulation plays an important role with respect to API permeation. Ibuprofen is reported to have a pKa value 4.4 (Dollery, 1999:I1); and by application of the Henderson-Hasselbach equation, at pH 5, 20.08% of ibuprofen will be present in its unionised form and at pH 7.4, 0.1% ibuprofen will exist in its unionised form. Since the unionised form of APIs is more lipid soluble than the ionised form, unionised forms of APIs permeate more readily across the lipid membranes (Surber & Smith, 2000:27). Therefore, it would be expected that ibuprofen formulated at pH 5 would be more permeable than formulations at pH 7.4. However, this did not correspond to the results (membrane studies) obtained in this study. It may be attributed to the solubility of ibuprofen in the different formulations. According to the pH-solubility profile of ibuprofen obtained in this study, it was more soluble at pH 7.4 than at pH 5. This was due to the fact that ibuprofen is a weak acidic compound, and for every 3 units away from the pKa-value, the solubility changes 10-fold (Mahato, 2007:14). However, with regard to the skin permeation studies, enhanced permeation was obtained with the formulations prepared at pH 5. This was in accordance with Corrigan et al., (2003:148) who stated that NSAIDs are less soluble and more permeable at low pH values, and more soluble and less permeable at high pH values. This was most probably due to the fact that unionised species, although possessing a lower aqueous solubility than the ionised species, resulted in enhanced skin permeation due to being more lipid-soluble. Finally, stability tests on the different semi-solid formulations for a period of three months at different temperature and humidity conditions were conducted to determine product stability. The formulations were stored at 25 °C/60% RH (relative humidity), 30 °C/60% RH and 40 °C/75% RH. Stability tests included: mass variation, pH, zeta potential, droplet size, visual appearance, assay, and viscosity. No significant change was observed for mass variation, pH, zeta potential and droplet size over the three months for any of the different formulations stored at the different storage conditions. In addition, no significant change in colour was observed for the gel and emulgel formulations at pH 5 and 7.4 over the three months at all the storage conditions. However, it was observed that the formulations containing Pheroid™ showed a drastic change in colour at all the storage conditions. This might have been due to oxidation of certain components present in the Pheroid™ system. Consequently, further investigation is necessary to find the cause of the discolouration and a method to prevent it. The gel formulated at pH 5 depicted the formation of crystals. This might have been due to the fact that the solubility of ibuprofen was exceeded, leading to it precipitating from the formulation. A possible contributing factor to the varying assay values obtained during the study might have been due to non-homogenous sample withdrawal. On the other hand, no significant change was observed for the emulgel and Pheroid™ emulgel formulated at pH 5 and 7.4. The emulgel and Pheroid™ emulgel formulated at pH 5 depicted relative instability (according to the International Conference on Harmonisation of Technical Requirements For Registration of Pharmaceuticals for Human Use, ICH) only at 40 °C/75% RH with a change in ibuprofen content of more than 5% (6.78 and 6.46%, respectively). The gel, emulgel and Pheroid™ emulgel at pH 7.4 exhibited the least variation in ibuprofen concentration at all of the storage conditions. This might indicate that the pH at which a semi-solid formulation is produced will have a direct influence on the stability of the product. No significant changes in viscosity (%RSD < 5) was observed for the gel and emulgel formulated at pH 7.4 and stored at 25 °C/60% RH. The remaining formulations at all of the specified storage conditions exhibited a significant change in viscosity (%RSD > 5) with a decrease in viscosity being more pronounced at the higher temperature and humidity storage conditions. A possible contributing factor to the change in viscosity over three months at the specified storage conditions might have been due to the use of Pluronic® F-127 (viscosity enhancer). This viscosity enhancer possesses a melting point of approximately 56 °C (BAST Corporation. s.a). The problem with this might have been the temperature (70 °C) at which the formulations were prepared. The higher preparation temperature might have caused the Pluronic® F-127 to degrade, thereby losing its ability to function appropriately. A balance must be maintained between optimum solubility and maximum stability (Pefile & Smith, 1997:148). Despite the lower skin permeation of the gel formulated at pH 7.4, this formulation performed the best, as it was considered stable (least variation during the 3 month stability test) and the obtained tape stripping results showed that this formulation depicted the highest ibuprofen concentrations in the stratum corneum and epidermis. Thus, topical as well as transdermal delivery were obtained. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease associated with high levels of tumour necrosis factor-alpha (TNF-a) in synovial fluid and synovial tissue (Saxne et al., 1989). Thalidomide is a proven inhibitor of the biological synthesis of TNF-a (Sampaio et al., 1991) and is believed to rely on this action for its suppression of the wasting of tissue which accompanies RA. Oral administration of thalidomide has proven to be effective in RA, but unacceptable side effects are easily provoked (Gutierrez-Rodriguez, 1984). Administration of thalidomide via the dermal route can down-regulate TNF-a production in and around the affected joint, and this without raising the systemic blood level to a problematical level. Based on thalidomide's physicochemical properties, it is unlikely that it can be delivered percutaneously at a dose required for RA. Therefore, we have embraced the idea of using N-alkyl analogues of thalidomide. The most important feature that an analogue of this compound might contribute is decreased crystallinity and increased lipophilicity. Ordinarily both these parameters should favour percutaneous delivery. The current study was primarily aimed at exploring the feasibility of percutaneous delivery of thalidomide and subsequently, three of its odd chain IV-alkyl analogues (methyl, propyl and pentyl) via physicochemical characterization and assessment of their innate abilities to diffuse through skin as an initial step towards developing a topical dosage form for the best compound. The biological activities, more specifically their potential to inhibit the production of TNF-a was determined for thalidomide and its N-alkyl analogues. In order to achieve the objectives, the study was undertaken by synthesizing and determining the physicochemical parameters of thalidomide and its N-alkyl analogues. A high level of crystallinity is expressed in the form of a high melting point and heat of fusion. This limits solubility itself, and thus also sets a limit on mass transfer across the skin. Generally, the greater a drug's innate tendency to dissolve, the more likely it is that the drug can be delivered at an appropriate rate across the skin (Ostrenga et al., 1971). Therefore, the melting points and heats of fusion were determined by differential scanning calorimetry. Aqueous solubility and the partition coefficient (relative solubility) are major determinants of a drug's dissolution, distribution and availability. N-octanollwater partition coefficients were determined at pH 6.4. Solubilities in water, a series of n-alcohols and mixed solvents were obtained, as well as the solubility parameters of the compounds in study. Secondly, in vitro permeation studies were performed from these solvents and vehicles using vertical Franz diffusion cells with human epidermal membranes. Thirdly, tumour necrosis factor-alpha (TNF-a) inhibition activities were assessed for thalidomide and its N-alkyl analogues. By adding a methyl group to the thalidomide structure, the melting point drops by over 100°C and, in this particular instance upon increasing the alkyl chain length to five -CH2- units the melting points decrease linearly. Heats of fusion decreased dramatically upon thalidomide's alkylation as well. Methylation of the thalidomide molecule enhanced the aqueous solubility 6-fold, but as the alkyl chain length is further extended from methyl to pentyl, the aqueous solubility decreased exponentially. The destabilization of the crystalline structure with increasing alkyl chain length led to an increase in lipophilicity and consequently an increase in solubility in nonpolar media. Log partition coefficients increased linearly with increasing alkyl chain length. Solubilities in a series of n-alcohols, methanol through dodecanol, were found to be in the order of pentyl > propyl > methyl > thalidomide. The N-alkyl analogues have more favourable physicochemical properties than thalidomide to be delivered percutaneously. The in vitro skin permeation data proved that the analogues can be delivered far easier than thalidomide itself. N-methyl thalidomide showed the highest steady-state flux through human skin from water, n-alcohols and combination vehicles. Thalidomide and its N-alkyl analogues were all active as TNF-a inhibitors. Finally, active as a TNF-a inhibitor, N-methyl thalidomide is the most promising candidate to be delivered percutaneously for treatment of rheumatoid arthritis, of those studied. / Thesis (PhD (Pharmaceutics))--PU for CHE, 1999.

Kidney bean proteins and peptides can be developed to serve as an important ingredient for the formulation of high quality foods or therapeutic products that may positively impact on body function and human health. The main goal of this thesis was to determine the in vitro structural and functional characteristics of major proteins and enzymatic protein hydrolysate of red kidney bean (Phaseolus vulgaris). Selective aammonium sulfate precipitation of the kidney bean proteins yielded 88% globulin and 7% albumin.The globulin and albumin are glycoproteins that contained ~4% and 45% carbohydrate contents, respectively. Physicochemical and functional characteristics of the globulin fraction, such as, gelation concentration, foam stability, emulsion capacity, and emulsion stability were superior to those of albumin. Reducing SDS-PAGE revealed vicilin with molecular weight of ~45 kDa as the major globulin in kidney beans. Circular dichroism spectroscopy of the purified vicilin showed reductions in α-helix, and β-pleated sheet conformations upon addition of NaCl or changes in pH. Likewise, the tertiary structures as observed from the near-UV CD spectra were also changed by shifts in pH conditions and NaCl addition. Far UV-CD showed increased β-sheet content up till 60oC from room temperature, but a steady loss in the tertiary structure as temperature was further increased; however, β-sheet structure was still detectable at 80oC. Differential scanning calorimetry thermograms showed a prominent endothermic peak with denaturation temperature at around 90oC, attributed to thermal denaturation of vicilin. Alcalase hydrolysis of kidney bean globulin produced multifunctional peptides that showed potential antihypertensive properties because of the in vitro inhibition of activities of renin and angiotensin I converting enzyme as well as the antioxidant properties. The <1 and 5-10 kDa peptide fractions exhibited highest (p<0.05) renin inhibition and the ability to scavenge 2, 2-Diphenyl-1-picrylhydrazyl free radical, inhibit peroxidation of linoleic acid and reduce Fe3+ to Fe2+. Based on this study, incorporation of kidney bean globulin as an ingredient may be useful for the manufacture of high quality food products. Likewise, the kidney bean protein hydrolysates, especially the <1 kDa fraction represent a potential source of bioactive peptides for the formulation of functional foods and nutraceuticals.

[pt] Resultados de testes preliminares para a reação de obtenção de formaldeído a partir de metóxi metano (DME) utilizando um catalisador Mo/SnO2 indicaram a necessidade de sistemas altamente ativos. Considerando-se que espécies dispersas de Mo parecem ser as mais efetivas para essa reação, e que a obtenção dessas espécies deve ser favorecida com o uso de um suporte de elevada área específica, estudou-se, neste trabalho, a influência dos parâmetros de síntese nas propriedades fisico-químicas do SnO2 preparado a partir de três diferentes métodos: a partir do ataque de Sn0 com HNO3, a partir da reação entre Sn+4 e NH4OH, e a partir da reação entre Sn+4 e dodecilamina. Foram realizadas alterações na forma de mistura das soluções, no tempo e na temperatura de reação, e na razão de aquecimento durante a calcinação. As amostras obtidas foram caracterizadas por adsorção de N2 para medições de área específica e distribuição de tamanho de poros, difração de raios-X e espectroscopia de reflectância difusa na região do UV-visível. Os resultados mostraram que todas as amostras obtidas são mesoporosas, embora apresentem diferentes valores de área específica, de tamanho de cristal, e de diferença de energia entre os orbitais HOMO-LUMO. Dentre os métodos estudados, o que partiu da reação entre Sn+4 e NH4OH apresentou maior sensibilidade às alterações realizadas, e as amostras assim obtidas apresentaram maiores valores de área específica; por outro lado, as amostras obtidas a partir do ataque de Sn0 com HNO3 não apresentaram variações texturais e estruturais significativas. Os resultados indicam ainda que, dentre os parâmetros alterados, a temperatura e o tempo da reação parecem ser os mais importantes. / [en] Preliminary tests on the reaction for formaldehyde production from metoxi methane (DME) using a Mo/SnO2 catalyst have indicated the necessity of highly active systems. Dispersed species of Mo seem to be the most effective for this reaction which may be favored by the use of a support of high specific area. Therefore the influence of the synthesis parameters on the physicochemical properties of the SnO2 has been studied in this work. This oxide has been prepared by three different methods: by the oxidation of Sn0 using HNO3, by the reaction of Sn+4 with NH4OH, and by the reaction of Sn+4 with dodecylamine. Variations on the way of mixing the solutions, on the time and the temperature of the reaction, and on the heating rate of the calcinations step have been carried out. These samples have been characterized by N2 adsorption for measurements of specific area and pore size distributions, X-ray diffraction and UV-visible diffuse reflectance spectroscopy. The results have shown that all samples are mesoporous even though they have exhibited distinct values of specific area, crystal size and HOMO-LUMO gap energy. The reaction of Sn+4 with NH4OH has presented the greatest sensitivity to the synthesis parameters, and it has provided samples with the highest specific area values. However the samples prepared by the oxidation of Sn0 using HNO3 have not been influenced. The results have also indicated that the temperature and the reaction time seem to be the most important parameters.

A utilização de polímeros naturais na produção de materiais biodegradáveis tem sido uma alternativa, uma vez que as embalagens produzidas com plásticos sintéticos se tornaram um problema ambiental por serem não-biodegradáveis. Neste trabalho, foi avaliada a capacidade filmogênica da farinha de chia (FC) e da sua mucilagem (MC), através de análises físico-químicas, mecânicas e estruturais. Os filmes comestíveis de FC foram incorporados de amido de milho (AM) em algumas formulações, sendo os mesmos elaborados na seguinte proporção de FC:AM, 1:0, 1:1 e 1:2 p/p, com 6 % p/v de sólidos totais, e com a mesma concentração de glicerol para todas as formulações testadas, 1 % p/v. Ao passo que os filmes de MC foram elaborados com 1 % p/v de MC, variando-se o nível de glicerol em 25, 50 e 75 % p/p (baseado no peso da MC). Ambos filmes biodegradáveis e comestíveis foram elaborados pela técnica de casting. Os filmes de FC apresentaram, nas diferentes formulações 1:0, 1:1 e 1:2 (FC:AM, p/p), as variações na espessura (de 0,247 a 0,194 mm), no conteúdo de umidade (de 12,23 a 7,27 %), na solubilidade (de 25,57 a 25,34 %), na permeabilidade ao vapor de água (de 0,567 a 0,293 g mm/kPa g m2), na resistência à tração (de 0,77 a 6,26 MPa), no alongamento (de 5,16 a 1,05 %), no módulo de Young (de 25,64 a 681,39 MPa), na força de perfuração (de 1,38 a 7,02 N) e na deformação na perfuração (de 1,03 a 1,42 %). Estes resultados demonstram que os filmes de FC obtiveram baixa solubilidade, baixa permeabilidade ao vapor da água, intermediária resistência à tração e baixo alongamento. Já os filmes de MC apresentaram, nas seguintes formulações CM25, CM50 e CM75, as variações na espessura (de 0,054 a 0,060 mm), no conteúdo de umidade (de 18,18 a 41,88 %), na solubilidade (de 52.74 a 84.50 %), na permeabilidade ao vapor de água (de 0,131 a 0,442 g mm/kPa g m2), na resistência à tração (de 17,75 a 9,44 MPa), no alongamento (de 1,93 a 15,89 %) e no módulo de Young (de 778,40 a 105,15 MPa). Estes resultados demonstram que a quantidade de glicerol nos filmes de MC interferiu significativamente em todos os atributos avaliados (p < 0,05). A medida que a concentração de glicerol aumentou, a permeabilidade ao vapor da água, o alongamento e a solubilidade do filme aumentaram, em contrapartida, a resistência à tração e o módulo de Young diminuíram. Além disso, os filmes de MC apresentaram baixa permeabilidade ao vapor da água, alta a intermediária resistência à tração e intermediário alongamento. Em relação à cor, os filmes de FC apresentaram coloração escura, a qual ficou mais clara à medida que se adicionou mais AM, além disso, apresentaram baixa a intermediária transparência. Já os filmes de MC, apresentaram cor levemente amarela-avermelhada, mas ainda transparente na aparência. Ambos filmes apresentaram excelente absorção da radiação ultravioleta, o que indica que os mesmos podem ter a capacidade de proteger os alimentos que sejam futuramente embalados pelos mesmos. Diante do exposto, o estudo demonstrou que, em geral, os filmes elaborados com a matéria-prima semente de chia (farinha e mucilagem) são promissores para serem utilizadas na produção de filmes comestíveis com especificações interessantes. / The use of natural polymers for the production of biodegradable materials has been an alternative, since packaging made with synthetic plastics have become an environmental problem due to they are non-biodegradable. In this study, it was evaluated the filmogenic capacity of chia flour (CF) and its mucilage (CM), through physicochemical, mechanical, and structural analysis. Corn starch (CS) was incorporated to some CF edible films, and were prepared in the following proportion of CF:CS, 1:0, 1:1 and 1:2 w/w, 6 % w/v of total solids, and the same glycerol concentration for all tested formulations, 1 % w/v. Whereas the CM films were prepared using 1 % w/v of CM, varying the level of glycerol in 25, 50 and 75 % w/w (based on CM weight). Both edible films were prepared by casting technique. The CF films presented, in the different formulations 1:0, 1:1 and 1:2 (CF: C:S, w/w), the variations in thickness (from 0.247 to 0.194 mm), in moisture content (from 12.23 to 7.27 %), in solubility (from 25.57 to 25.43 %), in water vapor permeability (from 0.567 to 0.293 g mm/kPa g m2), in tensile strength (from 0.77 to 6.26 MPa), in elongation at break (5.16 to 1.05 %), in Young's modulus (from 25.64 to 681.39 MPa), in puncture strength (from 1.38 to 7.02 N), and in puncture deformation (from 1.03 to 1.42 %). These results demonstrate that CF films showed low solubility, low water vapor permeability, intermediate tensile strength and low elongation at break. While the CM films presented, in the following formulations CM25, CM50 and CM75, variations in thickness (from 0.054 to 0.060 mm), in moisture content (18.18 to 41.88 %), in solubility (from 52.74 to 84.50 %), in water vapor permeability (0.131 to 0.442 g mm/kPa g m2), in tensile strength (17.75 to 9.44 MPa), in elongation at break (from 1.93 to 15.89 %) and in Young’s modulus (from 778.40 to 105.15 MPa). These results demonstrate that the amount of glycerol in the CM films caused significant differences in all tested attributes (p < 0.05). As glycerol concentration increased, water vapor permeability, elongation at break and solubility of CM films increased, whilst, tensile strength and Young's modulus decreased. Moreover, the CM films showed low water vapor permeability, high to intermediate tensile strength and intermediate elongation. Regarding the color, the CF films presented dark coloration, which became clearer as more CS was added, in addition, had low to intermediate transparency. While CM films presented slightly yellow-reddish color, but still transparent in appearance. Both films had excellent absorption of ultraviolet radiation, indicating that these films may have the ability to protect the foods that will be packed by them hereafter. This study revealed that, in general, the films produced with chia seed raw material (flour and mucilage) are promising for use in the production of edible films with interesting specifications.

O Brasil é o maior produtor mundial de suco de laranja e os resíduos gerados deste processamento representam sérios problemas ao meio ambiente. No entanto, estes resíduos podem ser considerados como subprodutos da indústria por possuírem elevado teor de fibras, possibilitando sua utilização como ingrediente em alimentos. As fibras podem ser adicionadas como substituto de gordura, resultando em produtos mais saudáveis. Neste sentido, este trabalho visa estudar a possibilidade e viabilidade do aproveitamento dos subprodutos da indústria de sucos de laranja para aplicação em alimentos. As fibras obtidas a partir dos subprodutos de laranja foram adicionadas como substituto de gordura em sorvetes e bolos. Foi realizada a caracterização físico-química e funcional das fibras, sendo também avaliados os compostos fenólicos e carotenoides presentes. As fibras foram submetidas a tratamentos como a hidrodestilação com o objetivo de reduzir o sabor amargo. Análises físico-químicas e sensoriais foram realizadas nos sorvetes e nos bolos. Duas amostras diferentes de fibra de laranja: F1 (casca, bagaço e sementes) e F2 (casca) foram analisadas sendo que ambas apresentaram alto teor de fibra dietética total e uma relação ideal entre fibra solúvel e insolúvel. A F2 apresentou os maiores teores de compostos fenólicos (125 mg/g) e carotenoides (1,21 mg/100 g) quando comparada a fibra F1. Essas fibras quando adicionadas ao sorvete de chocolate reduziram em média 70 % o teor de gordura, sem modificar propriedades sensoriais de cor, odor e textura, porém provocou efeitos negativos sobre o sabor e o sabor residual dos sorvetes. A adição de 1,0 % de fibra da casca de laranja, submetida à hidrodestilação, em sorvete de limão reduziu aproximadamente 50 % o teor de lipídeos das amostras e não modificou o conteúdo de proteína, as propriedades de cor, os valores de pH, os parâmetros de textura e não provocaram mudanças na aceitação dos atributos sensoriais do produto original. A fibra bruta da casca de laranja também pode ser considerada uma boa alternativa como substituto de gordura em bolos. Já que foram obtidas reduções de até 90 % no teor de lipídeos e até 27 % no valor calórico do produto. A adição de 3 % de fibra de laranja, não alterou a formulação do bolo de forma a modificar sua preferência perante os julgadores, mostrando resultados semelhantes em todos os parâmetros sensoriais comparativos ao bolo padrão. / Brazil is the world's largest orange juice producer and the wastes generated by this process represent serious environmental problem, however these residues may be regarded as byproducts of industry because their high fiber content allowing its use as ingredient in foods. Fibers can be added as fat replacer, resulting in healthier products. Thus, this work aimed to study the possibility and viability of orange juice industry byproducts utilization for application in foods. The fibers obtained from the orange juice byproducts were added as fat replacer in ice creams and cakes. The physicochemical and functional characterization of the fibers were performed, and carotenoids and phenolic compounds content were evaluated. The fibers were submitted to treatments such as hydro-distillation aiming to reduce the bitter taste. Chemical, physical and sensory analyses were performed in ice creams and cakes. Two different samples of orange fiber were analyzed: F1 (peel, pulp and seeds) and F2 (peel). Both samples showed high levels of total dietary fiber and an ideal ratio between soluble and insoluble fiber. The F2 showed higher levels of phenolic compounds (125 mg/g) and carotenoids (1.21 mg/100 g) when compared to fiber F1. The use of orange fiber as a fat replacer in ice cream led to a 70 % reduction of fat without causing significant changes on product attributes such as color, odor and texture, however caused negative effects on the taste and aftertaste of ice cream. The addition of 1 % of peel orange fiber, submitted to treatment by hydro-distillation, in lemon ice cream resulted in a mean reduction of approximately 50 % of the samples fat content and did not significantly modified properties as protein content, color properties, pH values, melt rate and texture parameters, and caused no changes in the acceptance attributes of original product. The crude peel orange fiber can be considered a good choice as a fat replacement in cakes, since the results showed 90 % reduction in lipid levels and 27 % in the caloric value of the product. The addition of 3 % orange fiber did not change the cake formulation in order to modify their preference before the judges, showing similar results in all sensory parameters comparable to standard cake.

Les performances des dispositifs photovoltaïques organiques (OPV) se sont considérablement améliorées au cours de la dernière décennie. Compte tenu de ces avancées, il est envisageable de transférer cette technologie développée au laboratoire à l’échelle industrielle. Le dépôt de la structure multicouche par le procédé d’impression jet d’encre est le moyen idéal de produire des dispositifs sur mesure, flexibles et potentiellement à faible coût. L’objectif de cette thèse a ainsi été de comprendre et de maitriser l’influence de la formulation des encres sur le procédé d’impression, en allant de l’éjection jusqu’aux performances photovoltaïques des couches imprimées. Les paramètres améliorant la qualité d’éjection ont tout d’abord été déterminés, puis ceux favorisant la mouillabilité. A partir de ces données, les encres ont été formulées pour que leurs propriétés physico-chimiques répondent à ces exigences. Ces nouvelles formulations ont ainsi permis d’optimiser la qualité d’éjection et d’assurer l’obtention d’une couche imprimée uniforme et compatible pour leur intégration en dispositifs OPV. Les couches obtenues après optimisation de la stratégie d’impression se sont avérées aussi performantes que celles réalisées par spin coating, procédé laboratoire de référence. Les avancées mises au point dans ces travaux, en termes de maitrise de la formulation et du procédé jet d’encre, ont contribué à l’amélioration de chacune des couches imprimées du dispositif. D’autre part, la méthodologie mise au point au cours de ce travail pourra s’appliquer à d’autres technologies photovoltaïques, ainsi qu’au domaine de l’électronique organique imprimée / The performances of organic photovoltaic devices (OPV) have been considerably improved over the last decade. These developments allow to scale up the technologies developed at the laboratory scale to the industrial one. For the elaboration of multilayered architectures, inkjet printing method is the ideal way to produce custom-made devices which could be also flexible and potentially low cost. The purpose of this PhD was to understand and to master the influence of ink formulation on the printing process, from the ejection step to the photovoltaic performance characterization of the printed layers. Parameters improving the ejection quality were first determined followed by those making the wettability easier. The inks have been then formulated to ensure that their physicochemical properties meet the aforementioned requirements. These new formulations enabled to optimize the quality of the ejection quality and to ensure uniform printed layers compatible with their integration in OPV devices. After optimization of the printing strategies, the obtained layers proved to be as efficient as those made by spin coating process (reference process at laboratory scale). The advances reached within in this work, in terms of formulations and processes, contributed to the improvement of each inkjet printed layers of the device. Furthermore, the methodology developed here could be applied in the near future either to other photovoltaic technologies and to organic printed electronics.

A utilização de polímeros naturais na produção de materiais biodegradáveis tem sido uma alternativa, uma vez que as embalagens produzidas com plásticos sintéticos se tornaram um problema ambiental por serem não-biodegradáveis. Neste trabalho, foi avaliada a capacidade filmogênica da farinha de chia (FC) e da sua mucilagem (MC), através de análises físico-químicas, mecânicas e estruturais. Os filmes comestíveis de FC foram incorporados de amido de milho (AM) em algumas formulações, sendo os mesmos elaborados na seguinte proporção de FC:AM, 1:0, 1:1 e 1:2 p/p, com 6 % p/v de sólidos totais, e com a mesma concentração de glicerol para todas as formulações testadas, 1 % p/v. Ao passo que os filmes de MC foram elaborados com 1 % p/v de MC, variando-se o nível de glicerol em 25, 50 e 75 % p/p (baseado no peso da MC). Ambos filmes biodegradáveis e comestíveis foram elaborados pela técnica de casting. Os filmes de FC apresentaram, nas diferentes formulações 1:0, 1:1 e 1:2 (FC:AM, p/p), as variações na espessura (de 0,247 a 0,194 mm), no conteúdo de umidade (de 12,23 a 7,27 %), na solubilidade (de 25,57 a 25,34 %), na permeabilidade ao vapor de água (de 0,567 a 0,293 g mm/kPa g m2), na resistência à tração (de 0,77 a 6,26 MPa), no alongamento (de 5,16 a 1,05 %), no módulo de Young (de 25,64 a 681,39 MPa), na força de perfuração (de 1,38 a 7,02 N) e na deformação na perfuração (de 1,03 a 1,42 %). Estes resultados demonstram que os filmes de FC obtiveram baixa solubilidade, baixa permeabilidade ao vapor da água, intermediária resistência à tração e baixo alongamento. Já os filmes de MC apresentaram, nas seguintes formulações CM25, CM50 e CM75, as variações na espessura (de 0,054 a 0,060 mm), no conteúdo de umidade (de 18,18 a 41,88 %), na solubilidade (de 52.74 a 84.50 %), na permeabilidade ao vapor de água (de 0,131 a 0,442 g mm/kPa g m2), na resistência à tração (de 17,75 a 9,44 MPa), no alongamento (de 1,93 a 15,89 %) e no módulo de Young (de 778,40 a 105,15 MPa). Estes resultados demonstram que a quantidade de glicerol nos filmes de MC interferiu significativamente em todos os atributos avaliados (p < 0,05). A medida que a concentração de glicerol aumentou, a permeabilidade ao vapor da água, o alongamento e a solubilidade do filme aumentaram, em contrapartida, a resistência à tração e o módulo de Young diminuíram. Além disso, os filmes de MC apresentaram baixa permeabilidade ao vapor da água, alta a intermediária resistência à tração e intermediário alongamento. Em relação à cor, os filmes de FC apresentaram coloração escura, a qual ficou mais clara à medida que se adicionou mais AM, além disso, apresentaram baixa a intermediária transparência. Já os filmes de MC, apresentaram cor levemente amarela-avermelhada, mas ainda transparente na aparência. Ambos filmes apresentaram excelente absorção da radiação ultravioleta, o que indica que os mesmos podem ter a capacidade de proteger os alimentos que sejam futuramente embalados pelos mesmos. Diante do exposto, o estudo demonstrou que, em geral, os filmes elaborados com a matéria-prima semente de chia (farinha e mucilagem) são promissores para serem utilizadas na produção de filmes comestíveis com especificações interessantes. / The use of natural polymers for the production of biodegradable materials has been an alternative, since packaging made with synthetic plastics have become an environmental problem due to they are non-biodegradable. In this study, it was evaluated the filmogenic capacity of chia flour (CF) and its mucilage (CM), through physicochemical, mechanical, and structural analysis. Corn starch (CS) was incorporated to some CF edible films, and were prepared in the following proportion of CF:CS, 1:0, 1:1 and 1:2 w/w, 6 % w/v of total solids, and the same glycerol concentration for all tested formulations, 1 % w/v. Whereas the CM films were prepared using 1 % w/v of CM, varying the level of glycerol in 25, 50 and 75 % w/w (based on CM weight). Both edible films were prepared by casting technique. The CF films presented, in the different formulations 1:0, 1:1 and 1:2 (CF: C:S, w/w), the variations in thickness (from 0.247 to 0.194 mm), in moisture content (from 12.23 to 7.27 %), in solubility (from 25.57 to 25.43 %), in water vapor permeability (from 0.567 to 0.293 g mm/kPa g m2), in tensile strength (from 0.77 to 6.26 MPa), in elongation at break (5.16 to 1.05 %), in Young's modulus (from 25.64 to 681.39 MPa), in puncture strength (from 1.38 to 7.02 N), and in puncture deformation (from 1.03 to 1.42 %). These results demonstrate that CF films showed low solubility, low water vapor permeability, intermediate tensile strength and low elongation at break. While the CM films presented, in the following formulations CM25, CM50 and CM75, variations in thickness (from 0.054 to 0.060 mm), in moisture content (18.18 to 41.88 %), in solubility (from 52.74 to 84.50 %), in water vapor permeability (0.131 to 0.442 g mm/kPa g m2), in tensile strength (17.75 to 9.44 MPa), in elongation at break (from 1.93 to 15.89 %) and in Young’s modulus (from 778.40 to 105.15 MPa). These results demonstrate that the amount of glycerol in the CM films caused significant differences in all tested attributes (p < 0.05). As glycerol concentration increased, water vapor permeability, elongation at break and solubility of CM films increased, whilst, tensile strength and Young's modulus decreased. Moreover, the CM films showed low water vapor permeability, high to intermediate tensile strength and intermediate elongation. Regarding the color, the CF films presented dark coloration, which became clearer as more CS was added, in addition, had low to intermediate transparency. While CM films presented slightly yellow-reddish color, but still transparent in appearance. Both films had excellent absorption of ultraviolet radiation, indicating that these films may have the ability to protect the foods that will be packed by them hereafter. This study revealed that, in general, the films produced with chia seed raw material (flour and mucilage) are promising for use in the production of edible films with interesting specifications.

O Brasil é o maior produtor mundial de suco de laranja e os resíduos gerados deste processamento representam sérios problemas ao meio ambiente. No entanto, estes resíduos podem ser considerados como subprodutos da indústria por possuírem elevado teor de fibras, possibilitando sua utilização como ingrediente em alimentos. As fibras podem ser adicionadas como substituto de gordura, resultando em produtos mais saudáveis. Neste sentido, este trabalho visa estudar a possibilidade e viabilidade do aproveitamento dos subprodutos da indústria de sucos de laranja para aplicação em alimentos. As fibras obtidas a partir dos subprodutos de laranja foram adicionadas como substituto de gordura em sorvetes e bolos. Foi realizada a caracterização físico-química e funcional das fibras, sendo também avaliados os compostos fenólicos e carotenoides presentes. As fibras foram submetidas a tratamentos como a hidrodestilação com o objetivo de reduzir o sabor amargo. Análises físico-químicas e sensoriais foram realizadas nos sorvetes e nos bolos. Duas amostras diferentes de fibra de laranja: F1 (casca, bagaço e sementes) e F2 (casca) foram analisadas sendo que ambas apresentaram alto teor de fibra dietética total e uma relação ideal entre fibra solúvel e insolúvel. A F2 apresentou os maiores teores de compostos fenólicos (125 mg/g) e carotenoides (1,21 mg/100 g) quando comparada a fibra F1. Essas fibras quando adicionadas ao sorvete de chocolate reduziram em média 70 % o teor de gordura, sem modificar propriedades sensoriais de cor, odor e textura, porém provocou efeitos negativos sobre o sabor e o sabor residual dos sorvetes. A adição de 1,0 % de fibra da casca de laranja, submetida à hidrodestilação, em sorvete de limão reduziu aproximadamente 50 % o teor de lipídeos das amostras e não modificou o conteúdo de proteína, as propriedades de cor, os valores de pH, os parâmetros de textura e não provocaram mudanças na aceitação dos atributos sensoriais do produto original. A fibra bruta da casca de laranja também pode ser considerada uma boa alternativa como substituto de gordura em bolos. Já que foram obtidas reduções de até 90 % no teor de lipídeos e até 27 % no valor calórico do produto. A adição de 3 % de fibra de laranja, não alterou a formulação do bolo de forma a modificar sua preferência perante os julgadores, mostrando resultados semelhantes em todos os parâmetros sensoriais comparativos ao bolo padrão. / Brazil is the world's largest orange juice producer and the wastes generated by this process represent serious environmental problem, however these residues may be regarded as byproducts of industry because their high fiber content allowing its use as ingredient in foods. Fibers can be added as fat replacer, resulting in healthier products. Thus, this work aimed to study the possibility and viability of orange juice industry byproducts utilization for application in foods. The fibers obtained from the orange juice byproducts were added as fat replacer in ice creams and cakes. The physicochemical and functional characterization of the fibers were performed, and carotenoids and phenolic compounds content were evaluated. The fibers were submitted to treatments such as hydro-distillation aiming to reduce the bitter taste. Chemical, physical and sensory analyses were performed in ice creams and cakes. Two different samples of orange fiber were analyzed: F1 (peel, pulp and seeds) and F2 (peel). Both samples showed high levels of total dietary fiber and an ideal ratio between soluble and insoluble fiber. The F2 showed higher levels of phenolic compounds (125 mg/g) and carotenoids (1.21 mg/100 g) when compared to fiber F1. The use of orange fiber as a fat replacer in ice cream led to a 70 % reduction of fat without causing significant changes on product attributes such as color, odor and texture, however caused negative effects on the taste and aftertaste of ice cream. The addition of 1 % of peel orange fiber, submitted to treatment by hydro-distillation, in lemon ice cream resulted in a mean reduction of approximately 50 % of the samples fat content and did not significantly modified properties as protein content, color properties, pH values, melt rate and texture parameters, and caused no changes in the acceptance attributes of original product. The crude peel orange fiber can be considered a good choice as a fat replacement in cakes, since the results showed 90 % reduction in lipid levels and 27 % in the caloric value of the product. The addition of 3 % orange fiber did not change the cake formulation in order to modify their preference before the judges, showing similar results in all sensory parameters comparable to standard cake.

O objetivo deste trabalho foi produzir pigmentos em pó a partir dos subprodutos de vinificação da uva tinta, variedade Bordô (Vitis labrusca), através da secagem em spray dryer utilizando maltodextrina como agente carreador. Foram estudados os efeitos das condições de processo sobre algumas propriedades físico-químicas, além da estabilidade e da atividade biológica do material obtido. Extratos etanólicos das cascas e sementes da uva foram obtidos e concentrados até um terço do volume inicial. Este extrato foi então misturado com o agente carreador maltodextrina 10 DE nas concentrações de 10, 20 ou 30% e atomizado em spray dryer, com vazão de alimentação de 44 mL/min e temperaturas do ar de entrada de 130, 150 ou 170°C, num total de nove ensaios. Além disso, foi obtida uma amostra de extrato concentrado liofilizado, sem a presença do agente carreador, para efeito de comparação. Avaliou-se o rendimento do processo de atomização; e para as amostras obtidas determinou-se o teor de umidade, retenção de antocianinas, higroscopicidade e solubilidade em água, a fim de verificar a influência das condições de processo sobre essas características. Estas amostras também foram avaliadas quanto à morfologia, distribuição do tamanho de partículas e isotermas de sorção de umidade. Todas as amostras obtidas (atomizadas e liofilizada) foram avaliadas quanto à cor instrumental, espectroscopia de infravermelho, estabilidade durante a estocagem, presença de compostos bioativos (fenólicos, flavonóides, antocianinas e proantocianidinas), além de atividade antioxidante, antimicrobiana e de inibição da arginase de Leishmania. As condições de processo avaliadas (temperatura de secagem e concentração de agente carreador) tiveram forte influência nas características estudadas. O teor de umidade, a retenção de antocianinas, a morfologia e o tamanho das partículas, foram bastante influenciados pela temperatura de secagem e pela concentração de agente carreador, enquanto que a higroscopicidade sofreu maior influência da concentração de agente carreador. Esse parâmetro também apresentou grande influência nas isotermas de sorção de umidade das amostras. Não houve grande interferência do processo de secagem na composição química do material obtido, evidenciada pelos espectros de infravermelho. Quanto à avaliação da estabilidade durante a estocagem, foi observado que as amostras contendo maltodextrina conservaram mais as antocianinas e a cor, quando comparadas com as amostras sem carreador e os extratos líquidos, indicando, que o processo de secagem e a presença do carreador, promoveram um efeito protetor aos compostos e sua cor. Todas as amostras apresentaram altos teores de flavonóides totais, antocianinas, proantocianidinas e elevados valores de atividade antioxidante variando de 314,06 a 441,04 &micro;molesTE/g de extrato seco pelo método DPPH e de 993,32 a 1138,68 &micro;molesTE/g de extrato seco pelo método FRAP. Apresentaram atividade antimicrobiana principalmente contra Staphylococcus aureus e Listeria monocytogenes. Além disso, tiveram grande capacidade de inibir a enzima arginase de Leishmania com porcentagem de inibição variando de 54,60 a 83,43%. Os resultados encontrados sugeriram que o processo de secagem em spray dryer com maltodextrina, dos extratos obtidos dos subprodutos da uva Bordô, produziu pós com diversas características interessantes, como baixa higroscopicidade, alta solubilidade e estabilidade, além de grande potencial biológico. Tais resultados evidenciam que este subproduto da indústria vinícola pode ser aproveitado como fonte natural de ingredientes funcionais. / The aim of this work was to produce powder pigments from grape byproducts of Bordo variety (Vitis labrusca) by spray drying using maltodextrin as carrier agent. The effects of process conditions on some physicochemical properties, stability and biological activity of the product were studied. Ethanol extracts were obtained from grape pomace (skins and seeds) and concentrated to one-third the initial volume. This extract was then mixed with the carrier agent 10 DE maltodextrin at concentrations of 10, 20 or 30% and atomized in a spray dryer, with feed flow rate of 44 mL/min and inlet drying air temperatures of 130, 150 or 170°C a total of nine tests. In addition, a sample of freeze-dried concentrated extract without carrier agent was obtained for comparison. It was evaluated process yield and the samples obtained were initially evaluated for moisture content, anthocyanins retention, hygroscopicity and solubility in water, in order to verify the influence of process conditions on these characteristics. These samples were also evaluated for morphology, particle size distribution and moisture sorption isotherms. All samples (spray-dried powders and freeze-dried extract) were evaluated for instrumental color, infrared spectroscopy, stability during storage, presence of bioactive compounds (phenols, flavonoids, anthocyanins and proanthocyanidins) plus antioxidant activity, antimicrobial activity and inhibition of Leishmania arginase. Process conditions evaluated (inlet drying air temperature and carrier agent concentration) had a strong influence on the characteristics studied. The moisture content, anthocyanin retention, morphology and particle size of the samples were strongly influenced by drying temperature and carrier agent concentration while the hygroscopicity suffered greater influence of the carrier agent concentration. The concentration of carrier agent also had great influence on the moisture sorption isotherms of the samples. There was no significant interference of the drying process on the chemical composition of the material evidenced by infrared spectroscopy. Regarding the evaluation of stability during storage, it was observed that the samples containing maltodextrin, retained much more anthocyanins and original color when compared with the sample without a carrier or liquid extracts, indicating both, the drying process and the presence of carrier, promoted a protective effect to the compounds and its color. All samples showed high levels of flavonoids, anthocyanins, proanthocyanidins and high levels of antioxidant activity ranging from 314.06 to 441.04 &micro;molTE/g of extract (dry weight), by DPPH and 993.32 to 1138.68 &micro;molTE/g of extract (dry weight) by FRAP method. Most samples showed antimicrobial activity against Staphylococcus aureus and Listeria monocytogenes. Moreover, had great ability to inhibit the enzyme arginase of Leishmania with inhibition percentage ranging from 54.60 to 83.43%. The results suggest that the drying process of Bordo grape pomace extracts in a spray dryer with maltodextrin, produced powders with various interesting characteristics such as low hygroscopicity, high solubility and stability, and large biological potential. This shows that this byproduct of wine industry can be used as a natural source of functional ingredients.