Nanotechnological delivery systems for the oral administration of active molecules: Polymeric microparticles and microemulsions applied to anti-inflammatory and anti-infectious drugs

This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit® S- 100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spraydried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on mediumchain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophiliclipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 μg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB

Anfotericina b pré-aquecida: um novo sistema terapêutico para infecções fúngicas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Otimização de solução extrativa e desenvolvimento tecnológico de produto seco por aspersão de Psidium guajava L.

The increasing in the consumption of plant medicine by parts of the population generated a bigger need for studies. Drug substitutions, changes and adulterations at the production techniques are common places at plant-originated drugs trade, leading governmental departments of drug control round the world to adopt many analytical practices to medicinal plants. However, agronomic and technological issues cause characteristics and chemical composition variation at the drug, problem to be solved by the subject researchers. The present work aims to obtain a spray dried extract from a extractive solution obtained from Psidium guajava L. leaves based in book references that stress the intermediate dosage forms advantages. It also tries to validate useful methodologies for the quality control for both raw material and its derivates. Using eight sets of the spray dried extract (with Eudragit®, Aerosil ® e Avicel PH101 ® as drying adjuvants), the study proposes analytical methods using techniques commonly performed to plant medicines and its intermediate forms. As results, a viable spray-dried extract was obtained from a standartized extract solution. Among the studied adjuvants, the combination Aerosil ® with Eudragit ® showed the drying outcome, rheology, humidity and tannin content values that best fitted the demands of the Brazilian Pharmacopaea

Micropartículas poliméricas à base de xilana e Eudragit® S-100 contendo mesalazina visando à liberação cólon-específica

Colon-specific drug delivery systems have attracted increasing attention from the pharmaceutical industry due to their ability of treating intestinal bowel diseases (IBD), which represent a public health problem in several countries. In spite of being considered a quite effective molecule for the treatment of IBD, mesalazine (5-ASA) is rapidly absorbed in the upper gastrointestinal tract and its systemic absorption leads to risks of adverse effects. The aim of this work was to develop a microparticulate system based on xylan and Eudragit® S- 100 (ES100) for colon-specific delivery of 5-ASA and evaluate the interaction between the polymers present in the systems. Additionaly, the physicochemical and rheological properties of xylan were also evaluated. Initially, xylan was extracted from corn cobs and characterized regarding the yield and rheological properties. Afterwards, 10 formulations were prepared in different xylan and ES100 weight ratios by spray-drying the polymer solutions in 0.6N NaOH and phosphate buffer pH 7.4. In addition, 3 formulations consisting of xylan microcapsules were produced by interfacial cross-linking polymerization and coated by ES100 by means of spray-drying in different polymer weight ratios of xylan and ES100. The microparticles were characterized regarding yield, morphology, homogeneity, visual aspect, crystallinity and thermal behavior. The polymer interaction was investigated by infrared spectroscopy. The extracted xylan was presented as a very fine and yellowish powder, with mean particle size smaller than 40μm. Regarding the rheological properties of xylan, they demonstrated that this polymer has a poor flow, low density and high cohesiveness. The microparticles obtained were shown to be spherical and aggregates could not be observed. They were found to present amorphous structure and have a very high thermal stability. The yield varied according to the polymer ratios. Moreover, it was confirmed that the interaction between xylan and ES100 occurs only by means of physical aggregation

Preparação e carcterização de complexos multicomponentes contendo ciclodextrinas e benznidazol

The benznidazole (BNZ) is the only alternative for Chagas disease treatment in Brazil. This drug has low solubility, which restricts its dissolution rate. Thus, the present work aimed to study the BNZ interactions in binary systems with beta cyclodextrin (β-CD) and hydroxypropyl-beta cyclodextrin (HP-β-CD), in order to increase the apparent aqueous solubility of drug. The influence of seven hydrophilic polymers, triethanolamine (TEA) and 1-methyl-2- pyrrolidone (NMP) in benznidazole apparent aqueous solubility, as well as the formation of inclusion complexes was also investigated. The interactions in solution were predicted and investigated using phase solubility diagram methodology, nuclear magnetic resonance of protons (RMN) and molecular modeling. Complexes were obtained in solid phase by spray drying and physicochemical characterization included the UV-Vis spectrophotometric spectroscopy in the infrared region, scanning electron microscopy, X-ray diffraction and dissolution drug test from the different systems. The increment on apparent aqueous solubility of drug was achieved with a linear type (AL) in presence of both cyclodextrins at different pH values. The hydrophilic polymers and 1-methyl-2-pyrrolidone contributes to the formation of inclusion complexes, while the triethanolamine decreased the complex stability constant (Kc). The log-linear model applied for solubility diagrams revealed that both triethanolamine and 1-methyl-2-pyrrolidone showed an action cosolvent (both solvents) and complexing (1-methyl-2-pyrrolidone). The best results were obtained with complexes involving 1-methyl-2-pyrrolidone and hydroxypropylbeta- cyclodextrin, with an increased of benznidazole solubility in 27.9 and 9.4 times, respectively. The complexes effectiveness was proven by dissolution tests, in which the ternary complexes and physical mixtures involving 1-methyl- 2-pyrrolidone and both cyclodextrins investigated showed better results, showing the potential use as novel pharmaceutical ingredient, that leads to increased benznidazole bioavailability

Produção, acúmulo e decomposição da serrapilhadeira e repartição da precipitação pluviométrica por espécies da caatinga

This study aimed to establish patterns of dynamics of litter and redistribution of rainfall of Caatinga vegetation. Sampling was done monthly for twenty three months in four areas: degraded, successional primary stage, secondary stage and late stage. We installed 72 collectors of 1.0 mx 1.0 m, with nylon fabric background in three areas. Litter deposited was fractionated into leaves, twigs, reproductive structures and miscellaneous, dried and weighed. To assess the stock of accumulated litter we used metal frame with dimensions of 0.5 mx 0.5 m, thrown randomly and collected monthly, taken to the laboratory for oven drying and weighed. To evaluate the decomposition, 40g of litter were placed in nylon bags (litterbags) mesh 1 mm ², dimensions 20.0 x 20.0 cm, being distributed on the soil surface and removed monthly, cleaned, dried and weighed. To evaluate the contribution of rainfall we used interceptometers installed 1.0 m above the ground surface, distributed under the canopy of six species of the caatinga, which evaluated the stemflow through collecting system installed around the stems of these species. The deposition of litter in the primary stage was 2.631,26 kg ha-1; 3.144,89 kg ha-1 in the secondary stage; 3.144,89 kg ha-1 in the late stage. The fraction of leaves was the largest contributor to the formation of litter in three stages. The degraded area showed greater accumulation of litter and decomposition has been sluggish during the dry period. We conclude that occurred greater litterfall in later stages. The late successional stage showed faster decomposition of litter, the evidence that is a better use of litter in nutrient cycling processes and incorporation of organic matter to the soil. The time required to decompose 50 % of the litter in the later stages of succession was lower indicating greater speed of release and reuse of nutrients by the vegetation. The specie jurema preta with less leaf area and consists of leaflets, showed greater internal precipitation in rain events of greater magnitude. The stemflow was not influenced by DAP and basal area. The water lost by trapping represented the largest proportion of total rainfall in all species studied

Iniqüidade em saúde: uma extensão das desigualdades sociais no sistema público de saúde do Brasil (2003-2006)

This issue analises the unevenness in the brazilian system of public health care as an extension of socials inequities. It is a theoretical study based in a historical method, using empirical camp from academic, corporation and institution researchs, along the period 2002-2006. Equality and effectiveness in health systems are analitical basic cathegories grap in the root of the doctrine, principles and organization of the Unique Health System, in which sectorial actions are inserted. Discuss the estructural prodution and determined those inequalities through some social determiners of health system: income, land, food securitiy, nutritional situation, basic sanitation, epidemiological inequities and public management policy. Carry out a thematic review over health social production, it formlation and the goals of social policies, as well as the insertion of the equality principle in the assistance system, in the frame of the running public health regulations. It uses reflections that enlighted the correlation between the process of political-institutional actions and equity on health assistance. Analized the pertinency of sectorial reorganizational strategies on basic attendance, confronting the hipothesis that those strategies reinforce social inequities in health system, because it organize diferential assistance levels over not equal baselines. The results show up that social inequalities, even remaining, have had a small decrease; that the selectiviness of actual public policies and the duplication of the health system, increases the differences within and between the social classes and configures the assistance as inequal. The basic care system has great shortages that also appeares in middle and complex assistance levels. As conclusion, it remarks that the health assintance system, even with it integrality has limits; structural problems on material conditions of living and health system could not be reversed only with institutional legal arragements; by the contrary, in border conditions, these strategies produce policies that reinforce inequities, neglecting the equity principle of the system in which frame, they work. One patina of this tim

Obtenção de insumo farmacêutico a partir das folhas de Cissampelos sympodialis Eichl e seu efeito sobre mediadores inflamatórios relevantes para a asma

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Dispersões sólidas de sinvastatina: preparação, caracterização, no estado sólido utilizando técnicas emergentes e estudo de estabilidade

This thesis aimed to assess the increase in solubility of simvastatin (SINV) with solid dispersions using techniques such as kneading (MA), co-solvent evaporation (ES), melting carrier (FC) and spray dryer (SD). Soluplus (SOL), PEG 6000 (PEG), PVP K-30 (PVP) e sodium lauryl sulphate (LSS) were used as carriers. The solid dispersions containing PEG [PEG-2(SD)], Soluplus [SOL-2(MA)] and sodium lauryl sulphate [LSS-2(ES)] were presented with a greater increase in solubility (5.02, 5.60 and 5.43 times respectively); analyses by ANOVA between the three groups did not present significant difference (p<0.05). In the phase solubility study, the calculation of the Gibbs free energy (ΔG) revealed that the spontaneity of solubilisation of SINV occurred in the order SOL>PEG >PVP 75%>LSS, always 80%. The phase diagrams of PEG and LSS presented solubilization stoichiometry of type 1:1 (type AL). The diagrams with PVP and SOL tend to 1:2 stoichiometry (type AL + AP). The stability coefficients (Ks) of the phase diagrams revealed that the most stable reactions occurred with LSS and PVP. The solid dispersions were characterized by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), particle size distribution (PSD), near-infrared spectroscopy imaging (NIR-CI) and X-ray diffraction of the powder using the Topas software (PDRX-TOPAS). The solid dispersion PEG-2(SD) presented the greatest homogeneity and the lowest degree of crystallinity (18.2%). The accelerated stability study revealed that the solid dispersions are less stable than SINV, with PEG-2(SD) being the least stable, confirmed by FTIR and DSC. The analyses by PDRX-TOPAS revealed the amorphous character of the dispersions and the mechanism of increasing solubility

Dunas costeiras de Jenipabu: Status de conservação e diretrizes para restauração da vegetação

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Relações internacionais: o comércio exterior do Brasil e Rio Grande do Norte no período de 1999 a 2008

The period post-war promoted several changes in relations economic, political and social world. Since then, a new division international of labor has delineated, with the great growth of Asian countries. In the field of international relations, the world still appears to transition is not completed because the old institutions were not replaced by new ones and the power of the United States as a major capitalist country remains unshaken, even with the emergence and strengthening of new economic global blocs. With globalization, Brazil emerges with more intensity in the face of new issues global, although its share in transactions trade global hasn‟t changed accordingly. In this sense, the objective of this dissertation is to examine, in a descriptive and critical the development of international relations and trade of Brazil and Rio Grande do Norte with the main blocs in the world from 1999 to 2008. As a secondary objective: to identify the assumptions theoretical that underpinned the decisions governments of the FHC and Lula, in particular, the interference of these terms in international relations and foreign trade. Adopted as the procedure methodological the literature review of the subject, as well as collection and processing of the data of foreign trade. During the Cardoso government has undergone the substantial growth in imports, as part of the economic policy of anti-inflationary, generating large deficits trade. From the first to the second term, with the inflection of exchange rate policy the country has resumed surpluses trade. The choice of government of the autonomy participation increased the relative share of the traditional blocks in total foreign trade and reduced the share of MERCOSUL. In the Lula government, there is the maintenance of some elements of the economic policy of the previous government and the partial shift in the conduct of foreign policy, with the option of autonomy through diversification, raising its stake on the blocks and other emerging countries in total foreign trade Brazilian and reducing the contribution of the traditional blocks such as NAFTA and the European Union. A trend observed in the previous government and deepened in the Lula government was the growth in commodity exports and the decline of manufactured products, confirming the model of conservative insertion of Brazilian exports. The Rio Grande do Norte followed the trend Brazilian in the growth of foreign trade, including in participating conservative, given that the products exported by the state are basically coming from horticulture irrigated and agribusiness. However, in the aspect of destination export, the state followed trajectory distinct from that in the Lula government, with the deepening of trade relations with traditional blocks, especially with the European Union and NAFTA

Análise da Conformidade e Caracterização da Matéria- Prima Empregada na Fabricação de Blocos Cerâmicos na Região Metropolitana de Salvador

The potential market of the metropolitan area of Salvador accounts for the estimated consumption of roughly 800 million horizontally perforated extruded clay bricks a year. The growing demand of consumers along with the competitiveness of the structural ceramic sector has driven forward a number of recent efforts and investments towards improving the quality of structural ceramics. In this scenario, the present study focused on sampling and evaluating the conformity of 8-hole horizontally perforated extruded clay bricks manufactured by different plants (A, B and C) in the metropolitan area of Salvador. In addition, representative clay and sandy-clay materials were collected from each plant and characterized by conventional physical, chemical and mineralogical techniques. Finally, experimental compositions designated as A, B and C, according to the source, were prepared by mixing different contents of the raw materials collected in the plants, fired at different temperatures and characterized. The results revealed a series of non conformities regarding ABNT guidelines. The characterization of raw materials revealed the presence of kaolinite and ilite in concentrations ranging from 64 to 90 wt.% along with free quartz (10 - 25%). The sandy-clay samples consisted basically of kaolinite. All raw materials depicted low contents of organics, amorphous constituents, alkaline oxides and feldspar. An analysis of the firing behavior of all different ceramic compositions revealed that the linear contraction of composition A was rather significant considering the temperature range evaluated, and it justifies the significant dimensional non conformity that was shown by bricks made with the ceramic A

Influência da adição de rejeitos cerâmicos nas propriedades de cerâmica vermelha da região do Recôncavo Baiano

The study of the physical and mechanic properties is an analysis of unquestioned importance on the production of the ceramic materials. In the region of the Recôncavo Baiano, there are ceramic and small brick factories, that still use rudimentary techniques, where the necessity of characterization of raw materials is denounced by the quality of the final product. The present work has for objective to study the behavior of the clay proceeding from the region of the Recôncavo, between the cities of Candeias and Camaçari/Ba, with addition of 5, 10 and 15% by weight of brick scraps, trying to optimize the physic and mechanical properties of the final product, aiming a better possibility of being manufactured, mechanic resistance, low linear retraction and water absorption. The brick scraps and the clay were characterized by FRX, DRX, TG, ATD and the granulometric analysis. Samples for testing where prepared by uniaxial pressing at 25Mpa, in 60x20x5mm size. The evaluated technological properties were: linear retraction, water absorption, apparent porosity and flexural strength. The samples were burned in electric oven in the temperatures of 850º, 950º and 1050ºC and compared its mechanical properties and the gresification. With addition of 15% by weight of brick scraps and burning at 900º-1000ºC the samples showed properties superior to that clay

Aproveitamento de resíduo de caulim em cerâmica branca

The world market of Kaolin has been growing as new investments for better quality of materials have been applied. This market produces amounts of dross that are put in the environment in a wrong way, causing damages to it. Trying to reduce these damages, researches have been done in an attempt to use kaolin dross in ceramic. The disposal of kaolin dross in the environment by the industries of the states of Rio Grande do Norte and Paraiba have great impact in society. Usually this dross is disposed clandestinely in places like roads, river banks and lands of small cities. The present work shows the characteristics of the kaolin produced by the mining company in Junco do Seridó, Paraiba state, western Seridó, 300 km from Natal, in the border of both states. After that, researches were done to study its physical and the chemistry characteristics, trying to see if it can be used in white ceramic. The samples got were bolted in fabric of 325# . The technological characteristics tried to use it as a product in white ceramic. For that, it was made a haracterization of the subject matter through enlargement analyses, ATG and ATD, elaborating three formulations that were burned in four different temperatures, 1175, 1200, 1250 and 1300 degrees centigrade up to 30 minutes. After the burning, the subjects were submitted to water absorbing tests, linear retreating, apparent porosity, apparent specific mass, resistance to flexibility and MEV. For one of the mixtures it was obtained demanded properties for a semi porous material

Estudo da Potencialidade da produção de tijolos de adobe misturado com outros materiais: uma alternativa de baixo custo para a construção civil

The production of the red pottery brick, made traditionally with clay, is a technique that is already stabled. However, in spite of the little complexity that involves the conventional process of these bricks production, it are exposed to many problems that begin in the fase of exploration of the mines, the problems get worse because of the lack of the clay's characterization, and they continue through the steps of the dough preparation, conformation of the products, the drying and the burning process. The wastefulness is shown and so is the low quality of the material produced. Among other factors, the high use of energy in the burning makes the cost of this material inaccessible to the low income consumer. Besides this, the destruction of the environment around the mines and the use of native vegetation to produce wood - the most used fuel in the pottery industry - make serious environmental damage. The production technique of a new type of simple brick (adobe), that has low cost and no environmental damage, can be the viable altemative to lower the cost of this part of the civil construction, and, consequently, in the building of cheaper houses. In this paper, the results of the mechanical resistance of the adobe brick are shown, using in its composition, clay, natural vegetable fibers, cement and plaster in a process that is completely handcrafted and manual. It is intented to make clear that are possible alternatives to be put in practice, with the simple process, using "raw earth" that has been used in the construction of houses in thousands of years, trying to solve these severe problems. Analysis and tests were performed to find results that could prove the possibility of the utilization of this kind of material. Other studies are in progress, and the new researches are necessary to enrich this work, but it stays the certainty that there is potential to produce bricks from adobe, as an alternative that has low cost to civil construction