Validação de metodologia analítica para cápsulas magistrais e estudo de equivalência farmacêutica do Cloridrato de Metformina 850mg referência, genérico e similar

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, 2013.O cloridrato de metformina é um fármaco anti-hiperglicêmico indicado para tratamento da diabetes mellitus tipo 2, disponível sob as formas de comprimidos e cápsulas farmacêutica magistral. O setor magistral no Brasil vem se desenvolvendo a cada ano, representando um dos maiores mercados mundiais de medicamentos manipulados. Esse fato gera a crescente necessidade de monitorização da qualidade destes produtos, uma vez que ensaios de teor e de dissolução para a forma farmacêutica cápsulas não são contemplados em compêndios oficiais. Partindo do ponto que no Mercado Farmacêutico Brasileiro existe essa apresentação do cloridrato de metformina sendo dispensada em farmácias de manipulação, houve a necessidade de validar o método de análise e de dissolução para cápsulas do cloridrato de metformina 850 mg, sendo essa a dosagem mais prescrita na clínica médica. Considerando que não existe a apresentação de cápsulas industrializada do cloridrato de metformina, decidiu-se por ampliar a pesquisa realizando um estudo comparativo entre as formulações referência, genérico e similar disponíveis comercialmente, para verificar a bioequivalência entre eles, considerando que são fabricados por diferentes laboratórios. Os resultados mostraram que os métodos de análises e dissolução foram adequados para avaliação das cápsulas magistrais de cloridrato de metformina de 850 mg atendendo aos critérios de linearidade, especificidade, precisão, exatidão e robustez preconizada em normas e compêndios oficiais vigentes, logo podendo ser utilizados de modo seguro e confiável para controle de qualidade na rotina de farmácias de manipulação, assim como em indústrias farmacêuticas que possa a vir produzir essa apresentação do cloridrato de metformina. As condições selecionadas para o teste de dissolução foram 900 mL de tampão fosfato de potássio pH 6,8 como meio, utilizando o aparato 1, cesto de aço inoxidável, com velocidade de rotação de 100 rpm. Outro aspecto que foi avaliado foram os testes físicos e físico-químicos de identificação, determinação de peso, desintegração, dureza, friabilidade, teor e uniformidade de conteúdo nas formas farmacêuticas cápsulas e comprimidos, segundo a Farmacopeia Brasileira, 5ª edição. Todos os resultados destes testes físicos e físico-químicos para as diferentes formas farmacêuticas se apresentaram de acordo, exceto o teste de teor para as cápsulas magistrais de cloridrato de metformina 850 mg. Um parâmetro que também foi avaliado com relação às apresentações referência, genéricos e similares foi a determinação da cinética de dissolução dos comprimidos, aplicando os modelos matemáticos de Ordem zero, Primeira ordem e Higushi. Em relação à cinética de dissolução, todos os produtos se enquadraram no modelo de Higushi, quando utilizados pontos anteriores à presença de um patamar nos perfis de dissolução, critério esse que indica o término do processo de dissolução. Comparações dos perfis de dissolução dos produtos referência, genéricos e similares através da eficiência de dissolução aplicando o teste One-Way ANOVA também foi realizado. Os valores obtidos para a eficiência de dissolução foram de 84,28%, 84,50%, 71,60%, 82,43% e 82,32% para os produtos R, G1, G2, S1 e S2 respectivamente, onde a eficiência de dissolução do produto G2 apresentou diferença em todos os tempos analisados comparando a todos os outros produtos. Os fatores f 1 e f 2 foram calculados e não demonstraram similaridade entre os produtos R e G2. Portanto, o produto G2 não pode ser considerado equivalente farmacêutico em relação ao produto R. Com isso, concluiu-se que em alguns casos, um produto genérico, ou mesmo similar que está no mercado, pode apresentar variações significativas quanto à eficácia terapêutica quando comparado ao produto referência, o mesmo pode acontecer com produtos manipulados em farmácias, pois a exigência quanto ao controle de qualidade dessas formulações magistrais, difere dos produtos industrializados por seguir normas reguladoras diferentes e com um nível de exigência inferior ao produzido em indústrias farmacêuticas. ______________________________________________________________________________ ABSTRACTMetformin hydrochloride is an anti-hyperglycemic indicated for the treatment of diabetes mellitus type 2, available in the forms of tablets and manipulation pharmacy capsules. The manipulation sector in Brazil has been developing every year, representing one of the largest world markets for compounded drugs. This fact leads to increasing need for monitoring the quality of these products, since content assays and dissolution for the dosage form capsules are not included in official compendia. Starting from the point that the Brazilian Pharmaceutical Market is the presentation of metformin hydrochloride being dispensed from pharmacies, it was necessary to validate the method of analysis and dissolution for capsules of metformin hydrochloride 850 mg, which is the most commonly prescribed drug dosage medical clinic. Whereas there is no presentation of capsules industrialized metformin hydrochloride, it was decided to extend search conducting a comparative study between the reference product, similar and generic commercially available, to verify the bioequivalence between them, whereas they are manufactured by different laboratories. The results showed that the methods of analysis and dissolution were appropriate for evaluating the manipulation capsules metformin hydrochloride 850 mg given the criteria of linearity, specificity, precision, accuracy and robustness advocated in official compendia and regulations actual, so it can be used safe and reliable for the routine quality control of pharmacies, as well as in pharmaceutical industry that can come to this presentation of metformin hydrochloride. The conditions selected for the dissolution test were 900 mL of potassium phosphate buffer pH 6.8 as means using the apparatus 1, stainless steel basket with rotation speed of 100 rpm. Another aspect that was evaluated was the physical tests and physicochemical identification, determination of weight, disintegration, hardness, friability, content and content uniformity in capsules and tablets, according to Brazilian Pharmacopoeia, 5th edition. All results of these tests physical and physicochemical for different dosage forms are presented according except the test content for the manipulation capsules of metformin hydrochloride 850 mg. A parameter that was also assessed for the reference presentations, generic and similar was the determination of the kinetics of dissolution of tablets, applying mathematical models of zero order, first order and Higushi. Regarding the kinetics of dissolution, all products fitted in the model Higushi when used earlier points to the presence of threshold dissolution profiles, this criterion indicating the end of the dissolution process. Comparison of the dissolution profiles of the reference products, generic and similar dissolution efficiency by applying the One-Way ANOVA test was also performed. The values obtained for the dissolution efficiency were 84.28%, 84.50%, 71.60%, 82.43% and 82.32% for products R, G1, G2, S1 and S2, respectively, where dissolution efficiency product G2 significant difference in all periods analyzed comparing to all other products. The factors f1 and f2 were calculated and showed no similarity between the products R and G2. Therefore, the product G2 cannot be considered equivalent in relation to the pharmaceutical product R. Thus, it was concluded that in some cases, a generic product, or similar product, which is on the market may vary significantly as therapeutic efficacy when compared to the reference product, the same can happen with products handled in pharmacies as a requirement regarding the quality control of these manipulation formulations, different from manufactured products follow different regulatory standards and with a lower level of demand in the pharmaceutical industries produced

Wild dogs at stake: deforestation threatens the only Amazon endemic canid, the short-eared dog (Atelocynus microtis)

The persistent high deforestation rate and fragmentation of the Amazon forests are the main threats to their biodiversity. To anticipate and mitigate these threats, it is important to understand and predict how species respond to the rapidly changing landscape. The short-eared dog Atelocynus microtis is the only Amazon-endemic canid and one of the most understudied wild dogs worldwide. We investigated short-eared dog habitat associations on two spatial scales. First, we used the largest record database ever compiled for short-eared dogs in combination with species distribution models to map species habitat suitability, estimate its distribution range and predict shifts in species distribution in response to predicted deforestation across the entire Amazon (regional scale). Second, we used systematic camera trap surveys and occupancy models to investigate how forest cover and forest fragmentation affect the space use of this species in the Southern Brazilian Amazon (local scale). Species distribution models suggested that the short-eared dog potentially occurs over an extensive and continuous area, through most of the Amazon region south of the Amazon River. However, approximately 30% of the short-eared dog's current distribution is expected to be lost or suffer sharp declines in habitat suitability by 2027 (within three generations) due to forest loss. This proportion might reach 40% of the species distribution in unprotected areas and exceed 60% in some interfluves (i.e. portions of land separated by large rivers) of the Amazon basin. Our local-scale analysis indicated that the presence of forest positively affected short-eared dog space use, while the density of forest edges had a negative effect. Beyond shedding light on the ecology of the short-eared dog and refining its distribution range, our results stress that forest loss poses a serious threat to the conservation of the species in a short time frame. Hence, we propose a re-assessment of the short-eared dog's current IUCN Red List status (Near Threatened) based on findings presented here. Our study exemplifies how data can be integrated across sources and modelling procedures to improve our knowledge of relatively understudied species

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Amazon protected areas and its ability to protect stream-dwelling fish fauna

Large protected areas have been created in Brazilian Amazon intending to safeguard as much of its biodiversity as possible. Despite these intentions, such megareserves were created predominantly focusing on terrestrial organisms and ecosystems. Here, we assessed the ability of the current Brazilian Amazon protected areas network to efficiently safeguard its stream-dwelling fish fauna. Ecological niche models were built for 138 stream fish species using MaxEnt software. We performed a gap analysis and spatial prioritization under three different Amazon protected areas scenarios: (1) strictly protected areas (SPAs) only; (2) SPA plus sustainable use areas (SPA + SUA); and (3) SPA + SUA plus indigenous territories (SPA + SUA + IT). The species were classified according to their distribution range size and required representation targets. Widespread species usually had lower area under the curve (AUC) and true skill statistics (TSS) values, which would be expected for large and heterogeneous areas such as the Amazon. Only partial gap species were found, with 20% to 90% of required representation targets included in PAs, which was not enough for a complete protection. Most of the officially protected areas in the Brazilian Amazon do not correspond to areas with high direct conservation values for stream fishes, once the priority areas for these species conservation were outside the PAs, leaving a high portion of the regional vertebrate fauna inadequately protected. We conclude that fishes and other freshwater organisms and habitats should be explicitly included during systematic conservation planning in order to thoroughly protect the Brazilian Amazon biodiversity. © 2018 Elsevier Lt

História da educação no Brasil: a constituição histórica do campo (1880-1970)

O artigo aborda a constituição do campo da história da educação no Brasil de dois prismas. No primeiro, elabora um histórico da disciplina a partir de três pertencimentos: à tradição historiográfica do Instituto Histórico e Geográfico do Brasil (IHGB); às escolas de formação para o magistério e à produção acadêmica entre os anos 1940 e 1970. No segundo, enfoca os trabalhos realizados nos últimos 20 anos, apontando temas e períodos de interesse e abordagens teóricas mais recorrentes.<br>This article tackles on the structuring of the field of history of education in Brazil through two angles. The first one elaborates on the history of the discipline from three views: the historiographic tradition of the Historical and Geographical Institute of Brazil ( IHGB); the development of teacher's colleges and the academic production from 1940 to 1970. The second one, focus on works done during the last 20 years, pointing out to topics, periods of interest and the most recurrent theoretical approaches

NEOTROPICAL CARNIVORES: a data set on carnivore distribution in the Neotropics

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non-detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non-governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peer-reviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non-detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio-temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other large-scale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data

NEOTROPICAL ALIEN MAMMALS: a data set of occurrence and abundance of alien mammals in the Neotropics

Biological invasion is one of the main threats to native biodiversity. For a species to become invasive, it must be voluntarily or involuntarily introduced by humans into a nonnative habitat. Mammals were among first taxa to be introduced worldwide for game, meat, and labor, yet the number of species introduced in the Neotropics remains unknown. In this data set, we make available occurrence and abundance data on mammal species that (1) transposed a geographical barrier and (2) were voluntarily or involuntarily introduced by humans into the Neotropics. Our data set is composed of 73,738 historical and current georeferenced records on alien mammal species of which around 96% correspond to occurrence data on 77 species belonging to eight orders and 26 families. Data cover 26 continental countries in the Neotropics, ranging from Mexico and its frontier regions (southern Florida and coastal-central Florida in the southeast United States) to Argentina, Paraguay, Chile, and Uruguay, and the 13 countries of Caribbean islands. Our data set also includes neotropical species (e.g., Callithrix sp., Myocastor coypus, Nasua nasua) considered alien in particular areas of Neotropics. The most numerous species in terms of records are from Bos sp. (n = 37,782), Sus scrofa (n = 6,730), and Canis familiaris (n = 10,084); 17 species were represented by only one record (e.g., Syncerus caffer, Cervus timorensis, Cervus unicolor, Canis latrans). Primates have the highest number of species in the data set (n = 20 species), partly because of uncertainties regarding taxonomic identification of the genera Callithrix, which includes the species Callithrix aurita, Callithrix flaviceps, Callithrix geoffroyi, Callithrix jacchus, Callithrix kuhlii, Callithrix penicillata, and their hybrids. This unique data set will be a valuable source of information on invasion risk assessments, biodiversity redistribution and conservation-related research. There are no copyright restrictions. Please cite this data paper when using the data in publications. We also request that researchers and teachers inform us on how they are using the data

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans—anteaters, sloths, and armadillos—have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, 10 anteaters, and 6 sloths. Our data set includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the southern United States, Mexico, and Caribbean countries at the northern portion of the Neotropics, to the austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n = 5,941), and Cyclopes sp. have the fewest (n = 240). The armadillo species with the most data is Dasypus novemcinctus (n = 11,588), and the fewest data are recorded for Calyptophractus retusus (n = 33). With regard to sloth species, Bradypus variegatus has the most records (n = 962), and Bradypus pygmaeus has the fewest (n = 12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other data sets of Neotropical Series that will become available very soon (i.e., Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans data set. Please cite this data paper when using its data in publications. We also request that researchers and teachers inform us of how they are using these data