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

Avaliação da argila atapulgita para potencial uso como excipiente farmacêutico em formas sólidas

Clays are natural materials that have great potential for use as excipients for solid dosage forms. Palygorskite is a type of clay that has hydrophilic properties as well as a large surface area, which could contribute to the dissolution of drugs. Thus, the present study aims to evaluate the use of palygorskite clay, from Piaui (Northeast region of Brazil), as a pharmaceutical excipient for solid dosage forms, using rifampicin and isoniazid as the model drugs. The former is a poorly soluble drug often associated with isoniazid for tuberculosis treatment. Palygorskite was characterized by X-ray diffraction (XRD), X-ray fluorescence (XRF), particle size, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and specific surface area (BET). The rheological and technological properties of palygorskite were determined and compared to those of talc, magnesium stearate and Aersosil 200. Mixtures between drugs and palygorskite were analyzed by differential scanning calorimetry (DSC), thermogravimetric analysis (TG) combined with thermal analysis (DTA) and Fourier Transform Infrared Spectroscopy (FT-IR), where the results were compared with those of the individual compounds. In addition, dissolution studies of solid dispersions and capsules containing the drugs, mixed with either palygorskite or a mixture of talc and magnesium stearate, were performed. The results showed that palygorskite has small particles with a high surface area. Its rheological characteristics were better than those of others commonly used glidants and lubricants. There was no interaction between palygorskite and the drugs (rifampicin and isoniazid). Among the dispersions studied, the mixture with palygorskite (5%) showed the highest drug dissolution when compared to other excipients. The dissolution of the rifampicin capsules containing palygosrkite was faster in higher concentrations. However, these differences were statistically different only in the first minutes of the dissolution experiment. The dissolution profile of isoniazid was also statistically different on the initial part of the experiment. The formulations prepared with isoniazid and palygorskite showed higher drug dissolution, but it was in descending order of concentration. According to these results, the palygorskite clay used in this study has great potential for application as an excipient for solid dosage forms

Obtenção e caracterização de complexos de inclusão binários e ternários com praziquantel

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Preparação e caracterização de sistemas emulsionados lipidicos contendo praziquantel

Praziquantel (PRZ) is the main drug used for treatment of schistosomiasis in Brazil. It is administered by oral rout as tablets. However, has low aqueous solubility which limits this therapeutic success dosage form and availability of liquid forms. The emulsion systems have great potential and represent an interesting strategy to increase the solubility of drugs. The aim of study was the development and characterization of lipid-emulsified liquid systems of the type oil in water (O / W), the base of soybean oil as the internal phase stabilized by surfactants pair Tween® 80 and Span® 80, for improving the phase biopharmaceutical of PRZ. After selecting the best value of Hydrophilic-Lipophilic Balance (HLB = 11), the parameters of the preparation of the formulations were optimized emulsification technique. The emulsions were successfully obtained; the liquid forms provided exhibited Newtonian behavior and an increase in solubility of PRZ higher than 20 times. The accelerated stability study demonstrated the stability of the emulsions and the effect of cosurfactants investigated. The study of the dynamics of interaction between components in the diagram showed pseudoternary phase regions to obtain O/W emulsions, whereas the study of the interaction of the components and their effect on system structure and the efficiency of incorporation of the drug led to systems with an amount of soluble drug even higher (about 1.5%), which demonstrates the potential of this new input mainly for the treatment of schistosomiasis, which resulted in the filing of patent BR 10 2013 0004 55 3

Preparação e caracterização de complexos multicomponentes contendo ciclodextrinas com metotrexato

Conselho Nacional de Desenvolvimento Científico e Tecnológico

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

O princípio constitucional do desenvolvimento e a utilização de recursos hídricos na indústria de petróleo

As can be inferred by the title of its study The constitutional principle of sustainable development and the utilization of hidrical resources in the oil industry the transcribed pages are dedicated to the approach of the mentioned subjects which, despite being apparently different, will be shown intrinsically connected as goes by the study. The superation of this first step by the reader will lead to an important perception of the title: that the situation requires, urgently, a defined posture, a complete conduct change and, therefore, a modification of the paradigms currently establisheds. To brake barriers, modifying what is lived by, is the ultimate goal. For that, there is no unique path, linear, but there were broached the development themes, the hidrical resources theme and oil and natural gas industry at the necessary points to achieve, by the end, a comprehension for the Brazilian Federal Republic goals in the search for the application of these juridical norms. The ones whom lay down over this study shall notice that, more than a simple approach over these themes (which are still less worked and searched in Brazil), the heavy critic of an instituted and pacifically accepted reality, directly offensive of the constitutional principles. The debate evolves from punctual and specific aspects, it gains life, flies, searching how the juridical order equalizes the economic model to the environment defense. Standing by the possibility of conciliation among constitutional principles, the remodeling of an economic segment is defended, aligning it to the sustainable limits. Development, sustainable, becomes means and goals to the implementation of liberty, capacitating everyone to achieve their goals of life, their libertments, fruit of the inherent antagonism of the Constitution the sustainable development offers, while an axiological vector, a new reality to the economic order, turning it into a motriz element to the fortification of constitutional normative force and for the national development

O princípio constitucional da redução das desigualdades regionais e os campos maduro-marginais de petróleo: aspectos regulatórios e fiscais

Under the circumstances of the desestatization that penetrate Brazilian economy in the 90‟s, new features in the monopoly of oil by the Union were designed by the constitutional amendment number 9. of 1995. This deep change in the legal regime of oil sector brought the possibility of entrance to small and medium size producers in this industry, especially through the production activities developed in mature and marginal fields of oil, which are located mainly in northeast region of Brazil. Considering that the intervention of state over the economy finds its guidelines and limits in Federal Constitution disposals, the present work investigated in which way states regulation, mainly through taxation rules, has obeyed the constitutional regime in force, and specially, the reduction of regional inequalities principle. By mean, firstly, of an analysis of central concepts (mature fields, marginal fields, small and medium size producers) we observed that the imprecision over the conceptual aspect has constituted an obstacle to a specific states‟ regulation, directed to this newborn class of producers, whose growth has been pursuit by the state. That is verified in the case of concession procedures, and also, concerning the taxation system applied to small and medium size producers. Examining the main constitutional principles related to this universe which are the legality, equality, privileged treatment to small enterprises, contributive capacity, and reduction of regional inequalities we conclude that it is legally possible, a truly specific regulation, including a special taxation regime, to the small and medium size producers whose activities are concentrate over mature-marginal fields, aiming the concretization of the Brazilian state main goals

Análise do processo judicial eletrônico (PJe) sob os parâmetros da discursividade processual e do acesso democrático à justiça

The conceptions of the judicial function, the process and the factors of legitimacy of the norm of decision are changed according to the model of State (liberal, social democratic and constitutional). The right of access to justice, likewise, follows the ideals present in constitutional movements experienced in different historical moments. The deficit of legitimacy of the judiciary is recurring subject of study in the doctrine, especially in the face of democratic standards that permeate the current paradigm of state. Under the process law, the essential element for the distinction of the states based on the rule of law (formal and material) and the democratic constitutional state lies in the democratic guarantee of participation to the litigants in the process of elaborating the norm of decision. The concern about the participatory democracy and the concretion of fundamental rights has as presupposition the conception of popular sovereignty. Keeping this effort in mind, the civil procedure cannot be oblivious to such considerations, especially when it justifies its constitutional conformation from the institutionalization of discourse within the procedural field (democratic principle) and of the democratization of access to justice, leading to the necessary contestation of the theory of instrumentality of the process. The democratic prospects of civil procedure and the concern about the legitimacy of the rule of decision cannot be moved away from the analysis of the judicial function and the elements that influence the legal suit s progress. The computerization of the judicial process entails extensive modification in the way the judicial function is developed, in view of automation of activities held, of the eliminating of bureaucratic tasks, manual and repetitive, and of streamlining the procedure. The objective of this study is to analyze the dogmatic changes and resulting practices from the implementation of the Judicial Electronic Process (JEP), prepared by the National Council of Justice, under the parameters of procedural discourse and democratic access to justice. Two hypotheses are raised, which, based on a bibliographic-documentary, applied and exploratory research, are contested dialectically. The expansion of publicity of procedural acts and the facilitating of communication and practice of such acts are elements that contribute to the effective participation of the recipients of the norm of decision in its making process and, therefore, the democratic principle in the procedural field. Ensuring access (to the parts) to the case files and reasonable duration of the process along with the preservation of its founding principles (contradictory, legal defense and isonomy) are essential to ensure democratic access to justice within the virtual system

Dignidade da pessoa humana e medidas sócio-educativas do Estatuto da Criança e do Adolescente

The main goal of this work is to verify the presence of the principle of human dignity, determined by the Constitution of 1988, when Socio Educational Acts from the Statute of Children and adolescent were put in practice, focusing on the treatment designated to the youth whose acts were against the law in the city of Natal, as well as the difficulties to match the legal texts and its reality. It is common knowledge that the law for children and adolescent was based in the principle of human dignity, for its institutes say so. But would the Law match the practice of Socio Educational Acts? Or this law would be an example of good intentions that never left the paper and became reality? First there is an approach on the human dignity principle, with its definition and limitation, according to a theory about the theme. Afterwards it is made a connection between human rights and the principle of human dignity considering historical and social features, for the law is also a reflect of these transformations, we try to show the different laws the country had until today, concerning the children inflicted by poverty and those whose acts were against the law, since the rodas dos expostos, the phase of irregular situation, in which the children were arrested simply because they were beggars, until present time. The theory aspects are shown beside a field research made with the adolescent and staff from CEDUC/Natal, producing a critical view about the subject and showing some solutions for the problems found. At last, it is made a critical analyses of the problems detected on the field research, and, in some cases, a suggestion is given to change the reality

A Constituição Federal de 1988 e a integração regional : o desafio da harmonização tributária

As an effect of the growing interdependence in international relations, regional integration was conceived to face globalization, with a remarkable influence in politics and law, since the first steps of the European experience. In Latin America, regional integration ideas have blossomed in the 60 s. Among its experiences, MERCOSUL is the one with the most advanced objectives. However, MERCOSUL has not managed to achieve the objectives planned nor moved forward the integration process. Differently of what happened in Europe, in MERCOSUL the common market projected is concluded. It faced many disappointments throughout its brief history. As it matters to law, those were caused by the absence of supranationality, a mechanism that would allow MERCOSUL s decisions to be directly binding in the States with no need of bureaucratic proceedings to incorporate them to national legal systems. Among Latin American States, Brazil is probably the most resistant to integration process, due to Federal Constitution 1988 rigidity and legal professionals conservadorism towards opening legal system to international law. In Brazil hermeneutical standards are always based on national sovereignty and international law is referred as less important. The problems become more visible relating to taxation, a subject that plays an enormous role in integration process for its economic impact, demanding the execution of tax harmonization policies compatible to the integration levels aspired. However, because of the large number of tax rules in the Federal Constitution, structural changes initiatives face difficulties in order to be implemented. Actually, after two Constitutional Reforms on taxation, Brazil has not yet succeeded on promoting the necessary adaptations to regional integration. The research has confirmed the hypothesis that supranationality has indispensably to be adopted if Brazil really desires to move forward the integration process. But it has also been demonstrated that there are hermeneutical paths suitable to the constitutional profile which allow the adoption of supranationality, through the revision of the sovereignty traditional concept

É como se tivesse a roça e faltasse a enxada: formação em serviço de professores de História no ensino sergipano

This thesis has the aim to comprehend the development of the superior graduation in life service and daily scholar of the history teachers in-land of Sergipe. The History Course graduation was realized through the second part of (Projeto de Qualificação Docente-PQD), the so-called, Teaching Qualification Project of the Federal University of Sergipe, first settled in 1998. Eight teachers were chosen for this research with more than (15) fifteen years of teaching in the Fundamental and Medium levels at public schools of our state (Sergipe). This empiric research priviledged oral testimony from them, which (ones) reveled about the memory tragetory of life. Since childhood until the History Course graduation, besides the evidence as Principal of schools as well as the following classes. All of them were interviewed from in-land and they are from very poor families with lack of social economical conditions. Those evidencies point out economic limitations in their different towns, that contributed to the continuous obstacle in the following studies, moreover in the common market. Therefore they still teach in order to believe in who´s at the botton of this business. Their testimony about this history graduation through PQD , gave them new Professional horizons, modifying their pedagogic practice, choosing what is worth into the social space beyond life expectancy. Through the analyses from all the documents and evidence in loco, it was evident that this graduation is not sufficient to change all the acting of teaching. Consequently, the lack of scholar situation still happens because this qualification doesn´t consider the knowledge of the teachers into their contexts. This research could also observe that besides the changing purposes in the suggested common-job by the globalization, the public politics education, is still underdeveloped in-land of Sergipe. According to the educational laws which obliges all tearches should be graduated, it could be observed that nothing changed into their acting. The old curricula don´t give them new possibility in their acting. At last their salaries, poor conditions in their common-job as well as the difficult ways to get to their pos graduation course still contributes to the underdeveloped acting before they´d graduated from the period before of their graduation

Saberes e práticas em experiência de construção da sustentabilidade no meio rural nordestino

The purpose of this work is to analyze the knowledge relationships that articulate in projects of maintainable rural development construction for the paraiban semi-arid, analyzing the farmers daily practices and their relationship with the technological practices spread by ONGs. We took as empirical object the rural community of Lajedo de Timbaúba, municipal district of Soledade-PB, located in the very small region of paraiban Curimataú. It is a community where registers one of the first cases of maintainable rural development planning in the state of Paraíba. The analysis was centered on the farmers experiences of life in sustainability experience, trying to understand how they acquire new knowledge and how they interact with them. In methodological terms, it was considered feasible to place the knowledge interaction between the farmers and technicians from ONGs by placing the analysis according to Paulo Freire s questioning (2006): extension or communication? To understand the farmers daily practices, it was resorted to the theoretical contribution by Michel de Certeau (2008) in order to discern a microresistance movement of inversion/rejection/changing by the farmers in relation to their external knowledge. Just from the theoretical point of view and resorting to the imaginary social by Cornelius Castoriadis (1982), it was considered the way of living of the farmers researched, having as reference the experience in the material and symbolic production of their lives. It became indispensable, therefore, not to dissociate the knowledge relationships between farmers and technicians from ONGs from the sustainability concepts, maintainable rural development, and rural extension. The results of the study revealed that the farmers from Lajedo de Timbaúba while dealing with the technological practices proposed by ONGs that work in the community, express those practices from their daily logic, and they constitute them in survival strategies that are inserted in their own idiosyncrasy. It was verified, therefore, that the external knowledge presented by the proposals of sociability alternatives with the droughts in the perspective of maintainable development while placed in the farmers daily relationship, they are judged as advantageous or disadvantageous when they are confronted with their peculiar way of doing their daily work. The technological practices are incorporated, denied, or recreated starting from evaluative criteria related to the preservation of the soil and to the economical and social reproduction of the unit of production of family agriculture

Uma intervenção educativa para profissionais de saúde na prevenção de pneumonia associada à ventilação mecânica

Quasi-experimental study, prospective with quantitative approach, performed at the Hospital do Coração in Natal, aimed at verified the existence of difference between the care given by health professionals to the patients under mechanical ventilation (MV) in the Intensive Care Unit, before and after an educative intervention. The population was of 31 professionals, with data collected between november 05 of 2007 to march 27 of 2008. The results show a yong population, female gender, middle level of education, nursing technique, working between 05 and 09 years on nursing profession, and 01 to 04 years on Intensive Care Unit; almost all, never had an kind of training over prevent pneumonia associated to mechanical ventilation; from those that had training, occur on the work place with duration from 12 to 24 hours. About endotracheal intubation, the cuff was tested with a sterilized syringe had a positive change after a educative intervention, increased from 75,0% to 100,0%; the sterile guide was used on 75,0% before and 100,0% after an educative intervention. Regarding endotracheal suction procedure, was not informed to the patient on 72,7% before, however was informed on 56,7% after; the hands was not previously washed 68,5% before, however was 63,3% after the procedure; mask was used on 74,2 % opportunities before and 76,7% after; the aspiration catheter had adequated size on 98,9% observation before and 100,0% after; the gaze was sterilized on 95,7% before and 100,0% after; the ventilator was connected to the patient during the aspiration intervals on 94,4% observation before and 100,0% after; the ambu bag was clean and protected on 76,1% before and 85,7% after; the aspiration catheter was discarded after be used on 98,9% before and 100,0% after; FIO2 was turned to the begging value on 32,9% observation before and 12,0% after; before the procedure 71,9% professions washed their hands and 73,3% after; before, notes of aspiration results were performed on 70,8% observation and 86,7% after. Regarding devices used on respiratory tract, aspirator flasks were not swapped on 84,6% observations before and 71,0% after; daily látex extention change was not performed on 93,6% observation before and 87,1% after; the ambu bag change was not performed on 50,0% observation before even if was duty or unprotected and on 75,8% opportunities was changed, after; nebulization was not prepared with sterile fluids or manipulated aseptically on 65,2% observation before, perhaps was on 71,7% after; before nebulizers were not changed on 65,2% observations, perhaps were on 60,9% after. Concerning ventilator breathing circuits, condense fluids cumulated on circuits were removed on 55,0% opportunities before, and 64,0% after; moisturizer was not filled with sterile water when already had small amount of liquid inside on 78,4% observations before, and 90,2% after; MV circuits were changed on 97,0% observations on presence of visible duty or when presents some kind of failure, before and 98,4% after. About body position, on 51,3% observations the decubitus position change were done before and 78,2% after; fowler position was maitened on 95,5% observations before and 98,2% after; Regarding respiratory physiotherapy, enteral diet was not interrupted before respiratory physiotherapy on 94,9% before and 90,0% after; respiratory physiotherapy devices were not disinfected or sterile on 69,6% observations before but they re on 60,0% after; before the cateter was not tested before introduction enteral diet or medications on 100,0% but after was done on 15,2%. About enteral feeding, intestine motility and measure of stomach contents were not done on 100,0% observations before, but was 15,2% after. We conclude that 05 of 07 valuated procedures in relation to MV, had a significant improvement on quality of care given after educative intervention, when compared before intervention

A pessoa idosa com doença crônica não transmissível atendida em serviços de média complexidade na cidade de Natal/RN

The demographic and epidemiological transition process caused by a declining in birth rates and in mortality, also changes occurred in morbidity and mortality is represented by the increasing of the aging population and the raising of chronic diseases. These diseases are characterized by multiple etiologies, risk factors, long latency period, a prolonged evolution, non-infectious origin and it has association with functional impairment and disability. Thus, elderly with chronic non-communicable disease has priority because they belong to a vulnerable group to get affection of comorbidities in aging, with increased demand and spending on health services. This study is aimed to analyse the understanding of elderly people with chronic non comunicable disease in the medium complexity service as a contribution to the improvement of health care in the city of Natal / RN. This is a descriptive and exploratory study with a quantitative approach, carried out at the Specialized Center for Elderly Health Care and at the Pescadores Hospital. The population was composed of 4,180 persons with a sample of 124 elderly aged above 60 years, attended in these medium complexity services. The instrument, a structured form, adapted from a questionnaire for monitoring risk and protective factors for chronic disease of the Ministry of Health. To collect data was was used the interview form containing demographic data, habits, health status and health care services. The results were processed using the Statistical Package for Social Science, version 18.0, analyzed by simple statistics. It was found that most seniors were female, predominantly between 70 and 74 years old, married, with a brown skin tone and Catholic religion, more than half had incomplete basic education, family income between one to two minimum wages and living with their families. Regarding the interviewers lifestyle, 94.4%, of them ate chicken and 97.6%, fruits, it was observed a reduction in smoking, alcoholism habits and physical activity according to the increasing age, 58.1 and 18.5% had insomnia18,5 % used sleeping pills. The elderly (51.6%) reported using services in times of sickness, seeking primary care at first (30.6%), 52% did not receive referral and was looking for free demand (38.7%). The most reported morbidity was hypertension, followed by musculoskeletal disorders. Regarding the difficulties in seeking health services, the delay in treatment and the waiting line were the most cited by the elderly. Almost all of them reported no activities to promote health in these services and those who received individual counseling on chronic diseases. Almost always, the health professionals who care of them, were mostly doctors followed by nurses. Based on the results presented, it is considered that the health services of medium complexity must undergone a more continuous dialogue with other attention level and focus on actions of health promotion and prevention. It is also recommended the necessity for qualified professionals to delivery health care to elderly and the implementation of protocols by a multidisciplinary health team, intending to provide better and continous care for the elderly with chronic diseases. The healthcare professionals who served them, were mostly physicians, followed by nurses. Through the results presented, it is considered that the medium complexity healthcare services need to perform a more continuous dialogue with the other levels of attention focusing attention to the health promotion and prevention actions. It is also recommended the necessity for qualified professionals to delivery healthcare for the elderly, in addition, a protocol implementation for the multidisciplinary health care team, to provide better care, and also the care continuity to elderly with chronic diseases