Influência de fármacos lipofílicos na estabilidade de emulsões de uso terapêutico

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Avaliação de um método de cromatografia em fase gasosa head space e estudo da estabilidade do etanol em amostras de sangue

The ethanol is the most overused psychoactive drug over the world; this fact makes it one of the main substances required in toxicological exams nowadays. The development of an analytical method, adaptation or implementation of a method known, involves a process of validation that estimates its efficiency in the laboratory routine and credibility of the method. The stability is defined as the ability of the sample of material to keep the initial value of a quantitative measure for a defined period within specific limits when stored under defined conditions. This study aimed to evaluate the method of Gas chromatography and study the stability of ethanol in blood samples, considering the variables time and temperature of storage, and the presence of preservative and, with that check if the conditions of conservation and storage used in this study maintain the quality of the sample and preserve the originally amount of analyte present. Blood samples were collected from 10 volunteers to evaluate the method and to study the stability of ethanol. For the evaluation of the method, part of the samples was added to known concentrations of ethanol. In the study of stability, the other side of the pool of blood was placed in two containers: one containing the preservative sodium fluoride 1% and the anticoagulant heparin and the other only heparin, was added ethanol at a concentration of 0.6 g/L, fractionated in two bottles, one being stored at 4ºC (refrigerator) and another at -20ºC (freezer), the tests were performed on the same day (time zero) and after 1, 3, 7, 14, 30 and 60 days of storage. The assessment found the difference in results during storage in relation to time zero. It used the technique of headspace associated with gas chromatography with the FID and capillary column with stationary phase of polyethylene. The best analysis of chromatographic conditions were: temperature of 50ºC (column), 150ºC (jet) and 250ºC (detector), with retention time for ethanol from 9.107 ± 0.026 and the tercbutanol (internal standard) of 8.170 ± 0.081 minutes, the ethanol being separated properly from acetaldehyde, acetone, methanol and 2-propanol, which are potential interfering in the determination of ethanol. The technique showed linearity in the concentration range of 0.01 and 3.2 g/L (0.8051 x + y = 0.6196; r2 = 0.999). The calibration curve showed the following equation of the line: y = x 0.7542 + 0.6545, with a linear correlation coefficient equal to 0.996. The average recovery was 100.2%, the coefficients of variation of accuracy and inter intra test showed values of up to 7.3%, the limit of detection and quantification was 0.01 g/L and showed coefficient of variation within the allowed. The analytical method evaluated in this study proved to be fast, efficient and practical, given the objective of this work satisfactorily. The study of stability has less than 20% difference in the response obtained under the conditions of storage and stipulated period, compared with the response obtained at time zero and at the significance level of 5%, no statistical difference in the concentration of ethanol was observed between analysis. The results reinforce the reliability of the method of gas chromatography and blood samples in search of ethanol, either in the toxicological, forensic, social or clinic

Estudo de compatibilidade e estabilidade térmica do ácido retinóico e hidroquinona por termogravimetria

Retinoic acid (RA) and hydroquinone (HQ) assets are widely used in pharmaceutical and cosmetic formulations, for having depigmenting properties and are largely produced in drugstores. To assist in the development of formulations containing the active RA and HQ National Forms of Brazilian Pharmacopoeia (2005 and 2012 ) proposes formulations with different excipients such as cetyl alcohol (AC), cetostearyl alcohol (ACT), methylparaben (MTP), propyl paraben ( PPB), glycerin (GLY), dipropylene glycol (DPG), imidazolidinil urea ( IMD ), cyclomethicone (CCM ), butylated hydroxytoluene (BHT), octyl stearate (ETO), EDTA, decil oleate (ODC) and hydroxipropymethyl celullose (HPMC). One of the difficulties found in most cosmetic formulations is the large number of incompatibilities between the components of the formulations, so the aim this study was to evaluate thermal stability and interactions between these active pharmaceutical ingredients and excipients. The depigmenting agents were analyzed by DSC and TG and excipients were analyzed by TG. The dynamic thermogravimetric curves were obtained on a SHIMADZU thermobalance, model DTG-60, using an alumina crucible, at the heating rate of 10ºC min-1, in the temperature range of 25-900 ºC, under an atmosphere of nitrogen at 50 mL min-1. The DSC curves were obtained using Shimadzu calorimeter, model DSC-60, using aluminum crucible, at the heating rate of 10ºC min-1, in the temperature range of 25-400ºC. The thermogravimetric and calorimetric curves were analyzed using TASYS software SHIMADZU. In this study no were found interactions between AR and the following excipients: MTP, PPB, IMD, ODC, EDTA, CCM, ETO, HPMC. However, were found interactions with the following excipients: AC, ACT, BHT, GLI and DPG. For HQ were found interactions with IMD and DPG. Interactions remained even changing proportions of the mixtures and the ternary. Thus, the studies conducted with excipients of National Formulary from 2005 and 2012 showed that these new excipients do not interact by thermogravimetry with the active pharmaceutical ingredients of this study

Produtividade, adaptabilidade e estabilidade fenotípica de cultivares de tomateiro sob diferentes condições de ambiente

O objetivo deste trabalho foi estudar o desempenho produtivo, adaptabilidade e estabilidade fenotípica de seis genótipos de tomateiro na região de Marília, SP. Os experimentos foram conduzidos em nove ambientes (seis sob condições de cultivo protegido e três sob condições de céu aberto), com seis genótipos (Carmen, Diva, Donador, Graziela, Vita e HE-295), em blocos casualizados, com quatro repetições. Ocorreram diferenças significativas entre ambientes, e a média geral dos cultivos protegidos superou a dos cultivos a céu aberto quanto à produtividade, apesar de a média geral dos cultivos a céu aberto ser superior quanto ao peso médio de frutos. As cultivares, à exceção de HE-295, demonstraram alta estabilidade, merecendo destaque as cultivares Carmen, Donador e Vita, que tiveram rendimento médio superior ao da média geral, adaptabilidade geral e comportamento previsível em todos os ambientes estudados. Quanto ao peso médio dos frutos, as cultivares Diva e Vita foram as únicas que mostraram ampla adaptabilidade a todos os ambientes, comportamento previsível, além de apresentarem peso médio do fruto superior ao da média geral.

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

Efetivação da garantia de defesa no estado constitucional de direito: colisão entre o poder punitivo e garantia de defesa

The domination of the violence for the Rule of law awakened a tension between the practice of the punitive power and the right to counsel. However, throughout the recent history of the Criminal law, this shock of forces has been determined for the punitive power. In this perspective, the present work intends to submit the guarantee of defense to a critical judgment, in search to conciliate its content to the Constitutional State of Right. For in such a way, it will be necessary to recognize the disequilibrium of the situation, but without considering the superiority of any of these elements. The State in such a way must fulfill the function to punish the culprits as to acquit the innocents. Despite the law is far from obtaining a harmonious speech, it is necessary that the defense guarantee coexists the punitive power as part of an only public interest, which is, to make criminal justice. In such a way, the existence of a sustainable balance between the punitive power and the guarantee of defense depend on the minimum interference of Criminal law and, also, of the judicial position in the concrete case. The present work faces, therefore, the moment of crisis of the Criminal law, consolidated with the advent of a new way of thinking according to the procedural guarantees, that will demand the overcoming of the old concepts. The Constitutional State of Right not only constitutes an efectiveness of the regime of the right to counsel, but in a similar way it searchs to accomplish the right of action and criminal justice as a whole. Knowing that the philosophy of the language raises doubts on the certainty, the truth and the judgement, it is imposed to understand that the defense guarantee is no more about a simple idea, but, in the crooked ways of the communication, we intend to find what the judge s function is when he faces this new reality

O princípio constitucional da livre concorrência como instrumento de desenvolvimento socioeconômico

The freedom of concurrence, firstly conceived as a simple market fundament in productive systems that recognized the productive forces freedom of action, appears as a clear instrument of protection and fomentation of the market, recognizing the importance of the simultaneous existence of various economic forces such the proper capitalism reason of constitution. It has, thus, a directly role linked to the fundamental idea that the market and its productive forces needed of a protection against itself, because it exists inside the market situations and circumstances, provoked or not, that could prejudice and even annihilate the its existence and functioning, whilst a complex role of productive forces presents at all economic creation space. It was the primacy of the classic liberalism, the first phase of the capitalism. The Constitutions, in that historic moment, did not proclaim any interference at the economic scenario, simply because it recognized the existence of an economic freedom prepared to justify and guarantee the market forces, with its own rules. Based on the structural changes that occurred at the following historic moments, inside the constitutionally recognized capitalism, it was verified changes in the ambit of treatment of the freedom of concurrence principle that, in a progressive way, passes to present a configuration more concerned with socialist and developing ideas, as long as not only a market guarantee. It emerges a freedom of concurrence which aim is instrumental, in relation to its objectives and constitutional direction as a role, and not anymore stagnant and with isolated treatment, in special at the constitutional systems the present s clear aspects of social interventions and guarantor of fundamental rights more extensive and harmonious. That change is located at a space of state actuation much more ample and juridical important, this time comprehending the necessity of managing the productive scenario aiming to reach a national social and economic development effectively guarantor of fundamental rights for all citizens. Those Constitutions take as point of starting that the social and economic development, and not only anymore the economic growth, is the effective way for concretization of these rights. In that way it needs to be observed and crystallized by political and juridical tools that respect the ideological fundamental spirit of the Constitutional Charters. In that scenario that seeks for solutions of rights accomplishment, in special the social rights, the constitutional principle of freedom of concurrence has been seen as an instrument for reaching bigger values and directives, such as the social justice, which only can be real at a State that can implement a comprehensive and permanent social and economic development. The freedom of concurrence tries to valorize and defend something larger and consonant to the political values expressed in the Constitutional Charters with social character, which is the right to a social and economical sustainable development, guarantor of more clear and compromised collective benefits with social justice. The origin of that constitutional imposition is not only supported by vague orientations of the economic space, but as integrated to it, with basis formed of normative and principles posted and prepared to produce effects at the proper reason of the Constitution

Ordem econômica e política nacional de recursos hídricos: hermenêutica constitucional para o desenvolvimento sustentável

This research proposes a study about the interpretative techniques application that are compatible with the national legal system under the principles for Sustainable Development characterized in Brazilian Constitution. It verifies the actual possibility of reconciliation between national development and environment protection, with reflections under the water legal protection. It was proposed, therefore, to point subsidies for jurisdictional decisions involving development and the environmental goods, protected as constitutionally guaranteed principles. It was assumed that, both development and environment protection represents basic rights that are eventually placed in conflict situations, considering the many legitimate economic activities within the Brazilian State. A representative case analysis was elected within the current national scene, detailing the judicial and political conflict involving the Transboundery water Project from the São Francisco River Basin to another Northeastern river basin in Brazil. The implementation of several constitutional principles with elements from legal hermeneutics provides subsidies for the legal analysis about the conflict between development and environmental protection. It was assumed that the main discussion item about rights due to development today is the institutions influence and their results, among them the rules, laws and interpretative elements for the constitutional text objectivity, as the institutions credibility and the Supreme Courts interpretations. The use of interpretative resources for specific conflict situations about constitutional principles by Superior Courts, on the search, would bring a contributory factor for decision safety, related to sustainable development principles, elimination of inequalities and regional protecting for the environment. Specific aspects of Law No. 9.433/97 that introduced the National Water Resources Policy were examined, with its instruments, in order to specifically contextualize aspects of the Brazilian water resources management politics

Acordos internacionais sobre a produção compartilhada de recursos naturais: a unitização interestatal na área do petróleo e gás sob o enfoque constitucional brasileiro

The apportionment of natural resources between sovereign States is a subject that relates many aspects of International law, as long as Constitutional Law, at the execution and application phases of international treaties that regulates the exploration of common goods. In this sense, because of their natural characteristics that creates an environment of constant migration and fixation in transboundary regions, terrestrial or maritime, the petroleum and the natural gas bound a complex juridical apparatus that can control the sovereign rights involved. This research is aim at accomplishing a study concerning the international agreements that enable the non-unilateral action, specifically the unitization treaties between sovereign States, as a manner to resolve situations related to the individualization of oil and/or gas reservoirs that go across their national borders. These agreements will be analyzed considering the international public law sources theory, bearing in mind yet the already existed experiences in this sense, not disregarding the way that this fact could affect Brazil. It will begin with an historical incursion over the unitization institute, covering its main characteristics and its formation and execution procedures, and finally it will address the Brazilian legal system and the comparative law threats the institute. The clauses of these relevant agreements will be analyzed in details, concerning its particularities and its contents. Because these agreements are international obligatory rules of law, it is indispensable that they are considered under the auspices of the international law system, focusing their nature and the subjects of international law and establishing them as sources of the international law, analyzing them, then, as international rules and the applicable law to these juridical relations, the conventional established, the consolidated international custom and the applicable International Law principles, appearing the State s responsibility as an important subject for the verification of the acts lawful practiced by States. The analysis of the apportionment of these natural resources ends with the individualization of possible exploitable marine oil fields located between the exclusive economic zone and the continental platform ends and the region administrated by the International Seabed Authority. At last, the Brazilian constitutional system appears as the mechanism of integration, application and execution of the international unitization agreements in Brazil, detaching the format and the proceedings that the international treaties take to acquire validity at the national legal system, passing through the treaties interpretation and the applicable constitutional principles, coming to its application in Brazil, considering the existing constitutional peculiarities and the role played by the National Agency of Petroleum, Natural Gas and bio-fuel ANP

Normas tributárias indutoras na concretização do princípio constitucional da redução das desigualdades sociais e regionais

The Federal Constitution states that the reduction of social and regional inequalities is one of the goals to be achieved by the Brasilian State. The economic constitution states that the national economy must be developed so as to achieve, amongst other objectives, the reduction of those inequalities. In this paper, we aim to demonstrate the duty, imposed by the Constitution to the State, of acting in the national economy so as to promote the achievement of the constitutional goals, among wich we highlight the reduction of inequalities. One of the instruments that can be used by the State to achieve this objective is its fiscal policy. It is also an aim in this paper to demonstrate that inducing tax norms can be used by the State, because it can encourage the economic agents to bring about the reduction of social and regional inequalities. Therefore, after bibliographic and jurisprudential research, we conclude that the duty, imposed to the State, of acting in the national economy so as to promote the achievement of the constitutional goals exists. We also conclude that this acting must be planed and constant, because the consequences are slow and that, within the limits of the constitution, the inducing tax norms can be an instrument for the State in order to reduct the social and regional inequalities

O princípio constitucional da redução das desigualdades regionais e o transporte de gás natural

In a country of continental dimensions as Brazil, one of the top challenges to its economic growth is the logistic related to energetical demand supply. We live now in the era of environmental protection and, in this new context of priorizations, it passes trough the search for alternative energies for the energetic matrix, due the petroleum elevated costs in the global market (and its finitude), but also due its pollution over the environment. This attempt of substitution needs solutions related to the national reality, into a national long term developing plan and based at a juridical-economic analysis of its realization. This study will look for, also based in an economical analysis, the juridical legitimity of choosing natural gas as the new protagonist of national economic growth (as a substitute of petroleum) and the necessary boost that must be done by law, based on an economic policy focused strictly for that fact, as a modifying agent of this reality. This study, therefore, will always be turned to a constitutional aspect, respecting the principles of economic order and the goal of reducing regional inequalities, which must influence the making off of a developing plan. At the end, it will try to demonstrate the juridical viability of such undertaking, tuned in jus-economical criteria. Another goal is related to the analysis of the natural gas industry, due the regulation of its transport has a major importance for national energetic integration, not only because this activity be characterized as a net industry, still under control of a natural monopoly, but also because the competitive or cooperative profile that should be priorized at the beginning of the economic planning for this activity (such as investment policies and its own rules that will submit private agents)

O regime constitucional da contribuição de intervenção do domínio econômico aplicável ao setor de combustíveis

The performance of the State in the economic area is only legitimized when to be given in virtue of the protection of the principles established constitutionally. Thus, the economic intervention of the State prioritizes the formation of a joust economic order and in this context, it fulfills to us to define, to the long one of this work, the contours of the intervention of the State in the economic domain in the presence of the Federal Constitution of the Republic of 05 of October of 1988, and, more specifically, in the petroliferous economic sector by means of the interventive contribution instituted after the Constitutional amendment 33/2001, with Law 10.336/2001. With the creation of this institute, in Brazil, emerged innumerable quarrels concerning its constitutional legitimacy, directing uncurling of the research to the study of the state intervention through this contribution and its constitutional limits, in the purpose to demonstrate the parameters for its institution and application. In this way, the interventive contribution in the fuel sector (CIDE-Combustíveis) shows itself as an intervention instrument on the economic domain, acting in way to finance the indirect performance of the State, specially in what concerns to the promotion of the principle of sustainable development principle. Therefore, CIDE-Combustíveis is an able instrument to concretizes the mentioned constitutional principle. Thus, the division of its incomes promotes the consolidation of the principle of the cooperative federalism. In this direction, from premises of the environmental tax law, this intends to demonstrate the utility and constitutionality of this exaction tax, primordially with regard to the realization of the basic right to the balanced environment

A construction como método concretizador de direitos fundamentais: aplicação na jurisdição constitucional brasileira

The way of organization of the constitutional jurisdiction implies the possibility to extend the democratization of the same one in function of the popular participation in the active legitimacy to constitutional process (procedimentalist model) e, at the same time, to assure technical viable decisions fast and to the complex problems of the constitucional law (substancialist model). The comparison with the constitutional jurisdiction of U.S.A. becomes interesting from the knowledge of the wide power to decide experience of Supreme the Court that for a methodology of construction of rights and not simply of interpretation of the Constitution, brought up to date and reconstructed throughout its historical evolution the direction of the norms of basic rights and the North American principles constitutional. Construction while constitutional hermeneutic method of substancialist matrix works with techniques as the measurement of principles, the protection of interests of minorities and the entailing of the basic rights with values politicians, what it can be brought to evidence of the Brazilian constitutional jurisdiction in order to improve the construction of basic rights that comes being carried through for the judicial ativism in control of the diffuse and abstract constitutionality. To define the limits of construction is to search, on the other hand, a dialogue with the procedimentalists thesis, aiming at the widening of the participation of the citizen in the construction of the basic rights for the constitutional process and to argue forms of the society to evaluate the pronounced decisions activist in the controls diffuse and abstract of constitutionality

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 do desenvolvimento sustentável: análise da sua concretização no Estado do Rio Grande do Norte

The Article 225 of Constitution of the Federative Republic of Brazil in its main body, stipulates that everyone is entitled to ecologically balanced environment and the use of common people and essential to the healthy quality of life, should be imposed on public authorities and the community the duty to defend it and preserve it for present and future generations. Following a universal trend, the letter raised the Brazilian environment the category of one of those values ideals of social order, dedicating it, along with a constitution of rules sparse, a chapter, itself, which definitely, institutionalized the right to healthy environment as a fundamental right of the individual. The national public policies and state should be in line with modern theories of Sustainable Development, outlined within the international society, and certainly instruments that should be made effective through the mobilization of civil society as a whole. The implementation of Human Rights, in fact, depends on a strong political action and not just a legal problem. Thus, this work of theoretical-descriptive nature we will address various dimensions of sustainable development, such as environmental education, water, sanitation, health and sustainable development plans, evaluating its current stage in our state