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It is mathematically shown that ductile fracture after finite plastic strain is a necessary consequence of the polycrystalline nature of the materials. A closed-form equation for the plastic strain to fracture of a fine-grained polycrystal with no voids is derived. The mathematical model for the plastic deformation is grounded on the physical hypothesis that adjacent grains slide with a relative velocity proportional to the local shear stress resolved in the plane of the shared grain boundary, when exceeds a finite threshold. Hence plastic flow is governed predominantly by the in-plane shear forces making grain boundaries to slide, and the induced local forces responsible for the continuous grain reshaping are much weaker. The process is shown to produce a monotonic hydrostatic pressure variation with strain that precludes a stationary flow. The hydrostatic pressure dependence on strain has two solutions. One of them leads to superplasticity, the other one is shown to diverge logarithmically at a finite fracture strain and then represents ductile behaviour. Emphasis is done in the mathematical aspects of the deformation of the polycrystal up to the initiation of fracture. Although theoretical predictions agree well with mechanical tests of commercial alloys, technical issues like the effects of the presence and evolution of porosity and other imperfections, or how fracture evolves after initiation are left for a more specific communication.

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The synergism between thermoresponsive and bioadhesive polymers can lead to the optimization of materials with enhanced mechanical and bioadhesive properties. Quality by Design can assure the understanding and control of formulation variables. In this approach, Design of Experiment has been widely utilized as an important strategy. Poly(methyl vinyl ether-alt-maleic anhydride) (PVMMA) is a bioadhesive polymer and Pluronic F127 (PF127) shows thermoresponsiveness. The association of these two polymers has been poorly investigated. The aim of this work was to study the mechanical, bioadhesive and rheological properties of polymer mixtures composed of PVMMA and PF127, in order to select the best conditions and formulations for biomedical applications. Textural properties (hardness, compressibility, adhesiveness, cohesiveness and elasticity), softness index, bioadhesion and rheological characteristics (flow and viscoelasticity) showed that 17.5-20% (w/w) PF127-polymer mixtures displayed improved values of the parameters. However, the rheological interaction parameter showed low synergism, due to the polymers' characteristics and system organization. The formulations displayed gelation temperatures suitable for administration, with improved bioadhesive properties mainly at 34 °C and suggests the formulations can be used for biomedical applications. DoE constituted an important tool to investigate these systems showing the main effects that significantly influence the binary mixtures.

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Polycarbophil is widely used in a variety of pharmaceutical formulations, mainly for their strong ability to adhere to the epithelial and mucous barriers (bio/mucoadhesion). On the other hand, its association with the thermoresponsive polymer (poloxamer 407) has been poorly explored. This work investigates the rheological, mechanical and mucoadhesive properties of polymer blends containing polycarbophil and poloxamer 407, in order to select the best formulations for biomedical and pharmaceutical applications. Mechanical (hardness, compressibility, adhesiveness, softness, and mucoadhesion) and rheological characteristics (consistency index, yield value and hysteresis area) showed that 20% (w/w) poloxamer 407- polymer blends exhibited higher values parameters. However, the rheological interaction parameter, which was more sensible than the mechanical interaction parameter, revealed higher synergism for systems comprising 15% (w/w) poloxamer 407, due to the system organization and polymers' properties. Furthermore, gelation temperatures were appropriated, suggesting that polymer blends can be used as biomedical materials, and displaying easy administration, enhanced retention and prolonged residence time at the site of application. Therefore, rheological, mechanical and mucoadhesive characterization provided a rational basis for selecting appropriated systems, useful for mucoadhesive drug delivery systems and biomedical applications.

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Black beans (Phaseolus vulgaris L.) are a rich source of flavonoids and saponins with proven health benefits. Spray dried black bean extract powders were used in different formulations for the production of nutraceutical capsules with reduced batch-to-batch weight variability. Factorial designs were used to find an adequate maltodextrin-extract ratio for the spray-drying process to produce black bean extract powders. Several flowability properties were used to determine composite flow index of produced powders. Powder containing 6% maltodextrin had the highest yield (78.6%) and the best recovery of flavonoids and saponins (>56% and >73%, respectively). The new complexes formed by the interaction of black bean powder with maltodextrin, microcrystalline cellulose 50 and starch exhibited not only bigger particles, but also a rougher structure than using only maltodextrin and starch as excipients. A drying process prior to capsule production improved powder flowability, increasing capsule weight and reducing variability. The formulation containing 25.0% of maltodextrin, 24.1% of microcrystalline cellulose 50, 50% of starch and 0.9% of magnesium stearate produced capsules with less than 2.5% weight variability. The spray drying technique is a feasible technique to produce good flow extract powders containing valuable phytochemicals and low cost excipients to reduce the end-product variability.

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A novel "Powder Solution Technology" involves absorption and adsorption efficiency which makes use of liquid medications, drug suspensions admixed with suitable carriers, coating materials and formulated into free flowing, dry looking, non adherent and compressible powder forms. Based upon a new mathematical model expression, improved flow characteristics and hardness of the formulation has been achieved by changing the proportion of Avicel ® PH 200 and Aerosil ® PH 200 from 50:1 ratio to 5:1 and in which the drug is dispersed in an almost molecularly state. Due to their significantly improved wetting properties a greater drug surface area is exposed to the dissolution media, resulting in an increased dissolution rate and bio availability. By using the Liquisolid technique, sustained drug delivery systems were developed for the water soluble drugs in which hydrophobic non-volatile solvents are used as vehicles.

A nova "Tecnologia da Solução Sólida" envolve eficiência de absorção e de adsorção, faz uso de medicações líquidas, suspensões de fármacos e misturas com transportadores adequados, materiais de cobertura e é formulada em formas sólidas em fluxo livre, secas, não aderentes e compressíveis. Com base em novo modelo matemático, características aprimoradas de fluxo e dureza da formulação foram alcançadas modificando-se a proporção de Avicel ® PH 200 e Aerosil ® PH 200 de 50:1 para 5:1, na qual o fármaco é disperso quase que no estado molecular. Devido às propriedades de umidificação significativamente aprimoradas e à área do fármaco exposta ao meio de dissolução, que resulta na velocidade de dissolução, a biodisponibilidade foi aumentada. Utilizando a técnica Liquisólido, desenvolveram-se sistemas de liberação controlada de fármacos solúveis em água, nos quais solventes hidrofóbicos não voláteis foram usados como veículos.

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