Avaliação do sistema conservante em formulação com extrato hidroalcóolico de schinus terebinthifolius raddi nacardiaceae

Schinus terebinthifolius Raddi is used in the treatment of skin and mucosal injuries, infections of respiratory, digestive and genitourinary systems. Currently one of the biggest problems faced for the industry of phytopharmaceuticals with regard to the quality of raw materials is the microbial contamination. The aim this study was to evaluate the antimicrobial action of the hidroalcoholic extract of aroeira, beyond testing the effectiveness of the preservative system in hidrogel to the base of this extract. The extracts were prepared by maceration in the ratio of 1:10 of solvent plant/with alcohol 40%. The methods for microbial count were pour plate and test for specific microorganisms, analyzing in third copy each one of the samples. The antimicrobial activity of aroeira extracts was performed using an agar diffusion method, using strains of S. aureus, P. aeruginosa, E. coli, B. subtilis, C. albicans, C. tropicalis, C. krusei, C. guilliermondii, T. rubrum, M. gypseum, A. flavus and A. niger. The formula with aroeira was evaluated by the challenge test. This method consisted of artificial contamination the sample with separate inóculos of A. niger, C. albicans, E. coli e S. aureus aeruginosa and determinations of survivors for the method of counting for pour plate , during times 0, 24h, 48h, 7 days, 14 days, 21 days and 28 days. How much to the results, one verified that the extract of aroeira in the 13,5 concentration mg/mL presented antimicrobial activity for cepas of E. coli, B. subtilis, P. aeruginosa e S. aureus, producing inhibition zone, on average with 13 mm of diameter. However it did not present no fungi activity. The formula with aroeira containig both methylparaben and propylparaben showed a good efficacy in challenge test front to strains of A. niger, C. albicans, E. coli, S. aureus. The A criteria of European Pharmacopoeia, adopted in this work, was verified that this product revealed the good preservative efficacy for the challenge test, time interval of the 28 days. However, it is interesting to extend this study, in order to carry through the sped up stability and the test of shelf, to establish the validity of this formularization

Estudo de pré-formulação para dose fixa combinada dos tuberculostáticos rifampicina, isoniazida, pirazinamida e etambutol (4 em 1)

According to the global framework regarding new cases of tuberculosis, Brazil appears at the 18th place. Thus, the Ministry of Health has defined this disease as a priority in the governmental policies. As a consequence, studies concerning treatment and prevention have increased. Fixed-dose combination formulations (FDC) are recognized as beneficial and are recommended by WHO, but they present instability and loss on rifampicin bioavailability. The main purpose of this work was to carry out a pre-formulation study with the schedule 1 tuberculosis treatment drugs: rifampicin, isoniazid, pyrazinamide and ethambutol and pharmaceutical excipients (lactose, cellulose, magnesium stearate and talc), in order to develop an FDC product (150 mg of rifampicin + 75 mg of isoniazid + 400 mg of pyrazinamide + 250 mg of ethambutol). The studies consisted of the determination of particle size and distribution (Ferret s diameter) and shape through optical microscopy, as well as rheological and technological properties (bulk and tapped densities, Hausner Factor, Carr s Index, repose angle and flux rate) and interactions among drugs and drug excipient through thermal analysis (DSC, DTA, TG and your derivate). The results showed that, except isoniazid, the other drugs presented poor rheological properties, determined by the physical characteristics of the particles: small size and rod like particles shape for rifampicin; rectangular shape for pyrazinamide and ethambutol, beyond its low density. The 4 drug mixture also not presented flowability, particularly that one containing drug quantity indicated for the formulation of FDC products. In this mixture, isoniazid, that has the best flowability, was added in a lower concentration. The addition of microcrystalline cellulose, magnesium stearate and talc to the drug mixtures improved flowability properties. In DSC analysis probable interactions among drugs were found, supporting the hypothesis of ethambutol and pyrazinamide catalysis of the rifampicin-isoniazid reaction resulting in 3- formylrifamycin isonicotinyl hydrazone (HYD) as a degradation product. In the mixtures containing lactose Supertab® DSC curves evidenced incompatibility among drugs and excipient. In the DSC curves of mixtures containing cellulose MC101®, magnesium stearate and talc, no alterations were observed comparing to the drug profiles. The TG/DTG of the binary and ternary mixtures curves showed different thermogravimetrics profiles relating that observed to the drug isolated, with the thermal decomposition early supporting the evidences of incompatibilities showed in the DSC and DTA curves

Determinação de parâmetros de qualidade para formas farmacêuticas homeopáticas

All medicine, whether allopathic or homeopathic, must go through strict quality control, which must ratify their characteristics throughout the period of validity. During the time of preparation and storage, solutions of the drugs are in permanent contact with packaging materials that can release undesirable substances to the solution. Several factors may influence the release of packing materials, and factorial design (FD) is a useful tool for analyzing the phenomenon. The aim of this study was the determination of quality parameters for Homeopathic solid (globules) and liquid (drops) dosage forms. It was carried out analysis in homeopathic globules for weight variation, mechanical strength, and moisture content uniformity. For liquid preparations, standard solutions were prepared from natural rubber bulbs, which were subjected to exhaustive extraction with two ethanol solutions (30 and 70%) in the ultrasonic bath for 20 minutes at 25°C and 50°C in three successive cycles. Studies of transfer have been made within five days, by spectrophotometric analysis in the UV region at 312 nm with λmáx and 323 nm for samples in 70% ethanol and 30% respectively. PH values were analyzed. We also conducted two FD studies, where the first, the three-level variables were solvent (chloroform, ethanol and nhexane), sample mass (30, 60 and 90mg), particle size (large disk, small disk and powder sample). In the second study, the solvent level variables were different ethanolic degrees (EtOH 30%, 70% and pure). The percentage of lending in the solutions was 5.5%, 12.4%, 24.2% and 41% of the total estimated in the reference solution. The values of rate constants of transfer were determined in the order of 0.0134 days-1 and 0.0232 days-1 in absorbance values, the solutions in ethanol at 30% and 70% respectively. These results suggest that the speed of transfer of materials from rubber is affected both by the nature of the vehicle as by the temperature

Otimização evalidação de métodos analíticos para a determinação simultânea de tuberculostáticos (4-FDC) por CLAE/DAD e CLUE/ DAD

Tuberculosis is a serious disease, but curable in practically 100% of new cases, since complied the principles of modern chemotherapy. Isoniazid (ISN), Rifampicin (RIF), Pyrazinamide (PYR) and Chloride Ethambutol (ETA) are considered first line drugs in the treatment of tuberculosis, by combining the highest level of efficiency with acceptable degree of toxicity. Concerning USP 33 - NF28 (2010) the chromatography analysis to 3 of 4 drugs (ISN, PYR and RIF) last in average 15 minutes and 10 minutes more to obtain the 4th drug (ETA) using a column and mobile phase mixture different, becoming its industrial application unfavorable. Thus, many studies have being carried out to minimize this problem. An alternative would use the UFLC, which is based with the same principles of HPLC, however it uses stationary phases with particles smaller than 2 μm. Therefore, this study goals to develop and validate new analytical methods to determine simultaneously the drugs by HPLC/DAD and UFLC/DAD. For this, a analytical screening was carried out, which verified that is necessary a gradient of mobile phase system A (acetate buffer:methanol 94:6 v/v) and B (acetate buffer:acetonitrile 55:45 v/v). Furthermore, to the development and optimization of the method in HPLC and UFLC, with achievement of the values of system suitability into the criteria limits required for both techniques, the validations have began. Standard solutions and tablets test solutions were prepared and injected into HPLC and UFLC, containing 0.008 mg/mL ISN, 0.043 mg/mL PYR, 0.030 mg.mL-1 ETA and 0.016 mg/mL RIF. The validation of analytical methods for HPLC and UFLC was carried out with the determination of specificity/selectivity, analytical curve, linearity, precision, limits of detection and quantification, accuracy and robustness. The methods were adequate for determination of 4 drugs separately without interfered with the others. Precise, due to the fact of the methods demonstrated since with the days variation, besides the repeatability, the values were into the level required by the regular agency. Linear (R> 0,99), once the methods were capable to demonstrate results directly proportional to the concentration of the analyte sample, within of specified range. Accurate, once the methods were capable to present values of variation coefficient and recovery percentage into the required limits (98 to 102%). The methods showed LOD and LOQ very low showing the high sensitivity of the methods for the four drugs. The robustness of the methods were evaluate, facing the temperature and flow changes, where they showed robustness just with the preview conditions established of temperature and flow, abrupt changes may influence with the results of methods

Caracterização térmica (TG/DTG, DTA, DSC, DSC-fotovisual) de Hormônios bioidênticos (estriol estradiol)

Bioidentical hormones are defined as compounds that have exactly the same chemical and molecular structure as hormones that are produced in the human body. It is believed that the use of hormones may be safer and more effective than the non-bioidentical hormones, because binding to receptors in the organism would be similar to the endogenous hormone. Bioidentical estrogens have been used in menopausal women, as an alternative to traditional hormone replacement therapy. Thermal data of these hormones are scarce in literature. Thermal analysis comprises a group of techniques that allows evaluating the physical-chemistry properties of a drug, while the drug is subjected to a controlled temperature programming. The thermal techniques are used in pharmaceutical studies for characterization of drugs, purity determination, polymorphism identification, compatibility and evaluation of stability. This study aims to characterize the bioidentical hormones estradiol and estriol through thermal techniques TG/DTG, DTA, DSC, DSC-photovisual. By the TG curves analysis was possible to calculated kinetic parameters for the samples. The kinetic data showed that there is good correlation in the different models used. For both estradiol and estriol, was found zero order reaction, which enabled the construction of the vapor pressure curves. Data from DTA and DSC curves of melting point and purity are the same of literature, showed relation with DSC-photovisual results. The analysis DTA curves showed the fusion event had the best linearity for both hormones. In the evaluation of possible degradation products, the analysis of the infrared shows no degradation products in the solid state

Avaliação in vitro da eficácia de produtos homeopáticos contendo momordica charantia através de bioensaios

Homeopathic medicines have been used for over two hundred years without the examination of their effects on in vivo and in vitro assays, due to the peculiarity of homeopathic preparations, the high dilution, which creates a challenge for the use of usual analytical techniques of quality control of medicine.Although there is scarcity of literature and variety of experiments, recently there have been some studies with few in vitro assays which have shown positive responses when evaluating the mechanism of action of homeopathic medicines which are able to act on a specific system.The present study aims to evaluate the efficacy of homeopathic products containing Momordica charantia through bioassays.Homeopathic products were tested by the MTT to assess cytotoxicity in RAW 264.7 (macrophage-like cells) and in tumor cells HeLa (human cervical adenocarcinoma cells), CHO K1 (Chinese hamster ovary cells), PANC-1 (human pancreas cancer cells) and PC-3 (human prostate cancer cells), dosage of inflammatory mediators NO, TNF-α and IL-6 released by RAW 264.7 cells, analysis of the death process and cell cycle changes of PC-3 by flow cytometry. The data demonstrate that homeopathic products of Momordica charantia did not show cytotoxicity to RAW 264.7, increased the production of inflammatory mediators by RAW 264.7 synergistically with LPS, showed cytotoxicity to PC-3 with change in its cell cycle inhibiting its proliferation, being the 30CH the most potent sample. Correlation studies were conducted in order to evaluate the possible in vitro applicable models to the quality control of homeopathic products with Momordica charantia. The data showed that the best applicable models in assessing the quality are the MTT to assess cytotoxicity in RAW 264.7 and PC-3 in 24 hours for Momordica charantia fruit products and dosage of NO production by RAW 264.7 with and without LPS

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

Contribuições sobre estudos térmicos (TG/DTG, DTA, DSC e DSC-Fotovisual) da rifampicina e seus principais produtos de degradação

Since its synthesis over 48 years rifampicin has been extensively studied. The literature reports the characterization of thermal events for rifampicin in nitrogen atmosphere, however, no characterization in synthetic air atmosphere. This paper aims to contribute to the thermal study of rifampicin through thermal (TG / DTG, DTA, DSC and DSC - FOTOVISUAL ) and non-thermal (HPLC, XRPD , IR - FTIR , PCA) and its main degradation products ( rifampicin quinone , rifampicin N-oxide 3- formylrifamicin). Rifampicin study was characterized as polymorph form II from techniques DSC, IR and XRPD. TG curves for rifampicin in synthetic air atmosphere showed higher thermal stability than those in N2, when analyzed Ti and Ea. There was characterized as overlapping events melting and recrystallization under N2 with weight loss in the TG curve, suggesting concomitant decomposition. Images DSCFotovisual showed no fusion event and showed darkening of the sample during analysis. The DTA curve in synthetic air atmosphere was visually different from DTA and DSC curves under N2, suggesting the absence of recrystallization and melting or presence only decomposition. The IV - FTIR analysis along with PCA analysis and HPLC and thermal data suggest that rifampicin for their fusion is concomitant decomposition of the sample in N2 and fusion events and recrystallization do not occur in synthetic air atmosphere. Decomposition products studied in an air atmosphere showed no melting event and presented simultaneously to the decomposition initiation of heating after process loss of water and / or solvent, varying the Ti initiating events. The Coats - Redfern , Madsudhanan , Van Krevelen and Herwitz - Mertzger kinetic parameters for samples , through the methods of OZAWA , in an atmosphere of synthetic air and / or N2 rifampicin proved more stable than its degradation products . The kinetic data showed good correlation between the different models employed. In this way we contribute to obtaining information that may assist studies of pharmaceutical compatibility and stability of substances

Desenvolvimento e validação de método analítico para determinação de WE010, WE014 e WE017

The synthetic guanylhydrazones WE010 (3,5-di-tert-butil-4-hidroxibenzaldehyde-guanylhydrazone), WE014 (4-bifenilcarboxialdehydeguanylhydrazone) and WE017 (3,4-diclorobenzaldehydeguanylhydrazone) showed high cytotoxic activity in terms of percentage inhibition of cancer cells growth. However, further progress in the development of these drug candidates requires precise and convenient methods for their qualitative and quantitative analyses. The aim of this study was to develop and validate High Performance Liquid Chromatography with diode-array detection (HPLC-DAD) and Ultra Fast Liquid Chromatography with diode-array detection (UFLC-DAD) methods suitable for as simultaneous as isolated determination of studied guanylhydrazones, based on the optimization of chromatographic parameters and obtaining reduced detection times. The chromatographic analyses of analytes by HPLC were performed on C18 ACE analytical column (150 mm x 4.6 mm), with a particle size of 5.0 μm. Among all the conditions assayed, the best results of separation were obtained with a mixture of methanol:water (60:40, v/v) as the mobile phase at a flow rate 1.5mL/min and pH of 3.5 adjusted at acetic acid. The UFLC method was developed by experimetal desing techniques in order to find optimal chromatographic analytical conditions, which were achieved on XR-ODS analytical column (50 mm x 3.0 mm), with a particle size of 2,2 μm, maintained at 25 ºC. The mobile phase was consisted of methanol:water (65:35, v/v) with 0.1% triethylamine (TEA) and pH of 3.5 adjusted at acetic acid, at a flow rate 0.5 mL/min. The procedure were validated following evaluating parameters such as specificity, linearity, limits of detection (LD) and quantification (LQ), precision, accuracy and robustness, giving results within the acceptable range. Although the UFLC method shows better sensitivity (lower values of LD and LQ), robustness (lower rates of relative standard deviation) and minimize spending time and solvent, both developed methods were adequately applied to the analysis of guanylhydrazones molecules, may be used in routine of quality control laboratories. Keywords: guanylhydrazones, HPLC/DAD, UFLC/DAD, validation of analitical method

Variabilidade genética e sensibilidade de acessos de Pistia stratiotes ao herbicida glyphosate

A alface-d'água (Pistia stratiotes) é uma das principais entre as macrófitas aquáticas que causam problemas em corpos hídricos no Brasil e são consideradas como plantas daninhas. O presente trabalho foi realizado com os objetivos de conhecer melhor a variabilidade genética dessa macrófita e relacionar essa variabilidade com a resposta à aplicação do herbicida glyphosate. Para isso, foram coletados indivíduos em 12 corpos hídricos em diferentes cidades do território nacional (Americana, Cambaratiba, Curitiba, Itapura, Jaboticabal, Lagoa Santa, Piraí, Rio Grande, Rubinéia, Salto Grande, Santa Gertrudes e Três Lagoas). Os acessos foram caracterizados pelo uso de marcadores RAPD (DNA Polimórfico Amplificado ao Acaso), que permitiram, com o auxílio de iniciadores aleatórios, a caracterização dos locos polimórficos identificados por uma matriz de ausência e presença de bandas. Utilizando essa matriz, a análise de agrupamento permitiu nítida classificação dos acessos em três grupos com diferenças genéticas entre eles. Um ensaio de controle químico, com plantas mantidas em vasos plásticos (5 L) e pulverizadas com o herbicida glyphosate nas concentrações de 0,0, 0,6, 1,2, 1,8 e 2,4 kg ha-1, identificou, utilizando avaliações aos 7, 14 e 21 dias após aplicação, que as duas maiores doses promoveram melhor efeito herbicida. Foi verificado também que os acessos de Curitiba e Cambaratiba apresentaram menor suscetibilidade ao herbicida glyphosate. Não houve correspondência entre a estrutura de grupos dos acessos pela análise multivariada de agrupamento com a técnica RAPD e a suscetibilidade da alface-d'água ao glyphosate.

Associativismo nos municípios rurais: uma alternativa de desenvolvimento local em Portalegre/RN

This work aims to study the associations as mediating the process of social change and its importance for local development. The hypothesis is that associations, but bring dynamism to the smaller cities and improve the living conditions of their members, relegated to the background social sustainability, understood this as a permanent exercise of mobilization and participation in community life. The assumptions of the study are that the practice group has influenced the processes of local development in Brazilian rural municipalities through the mediation of government programs and projects aimed at combating rural poverty require social organization for their achievement. The concept of local development in this work was rescued from studies of political economy and sociology. But the concepts of collective action and partnerships advêem studies of political participation and social development of the theory of alternative or solidarity. The party consisted of an empirical case study conducted with four associations of farmers in the municipality of Portalegre-RN. Why choose qualitative study was used the technique of semi-structured interviews with the chairmen I members of associations and other actors considered essential to understanding the study (religious leaders, local political power and chairman of the union of rural workers), a total of 20 interviews, in addition to the observations of field and documentary research in records of the.ir own organizations. The survey results show that the performance of groups of farmers are key components and determinants for the production I marketing of agricultural products and for boosting the economy, as well as security for minimum levels of citizenship. Yet we are still in a space purpose of social change, which comes to confirm the initial hypothesis of this work

O discurso religioso no processo migratório para o caldeirão do beato José Lourenço

The Caldeirão is a site located in the city of Crato, in the south of Ceará, belonged to priest Cícero Romão Batista. There, was created a religious community led by blessed José Lourenço, who marked the life of thousands of Northeast country people in 1930s, for represent to them a space of religious conviviality, work and devotion. The Caldeirão s population was about three thousand of people, originated from states of Pernambuco, Alagoas, Paraíba, Maranhão, Piauí, Ceará and Rio Grande do Norte, who share the community s daily activities. The misery caused by the dryness and exploration of these country people by the landlords are indicated as the motivator elements of this migratory flux by the greater number of works published about the Caldeirão, turning the community into a primitive experience of class struggles. This present study proposes other comprehension of this migratory movement by the religious speech of salvation taken to country people by the counselor Severino Tavares. Was used as analysis camp the remaining norte-rio-grandenses that migrated to the Caldeirão, and as theoretical and methodological references the understanding model of investigation, the cultural history and the remaining memorial speech analysis. The work follows that pointing the phenomenon of Caldeirão as an campestral revolt is try to impose to this people the aspirations or wishes of others, besides of deny to them the right and the dignity of act by their believes and their own dreams.

Prováveis consequências do abrandamento da metodologia de erradicação do cancro cítrico no Estado de São Paulo

Recentemente a Secretaria de Agricultura e Abastecimento do estado de São Paulo abrandou os critérios relacionados à erradicação do cancro cítrico. em abril de 2009 mais de 99,8% dos talhões comerciais de laranjeiras doces estavam livres da doença em São Paulo. Abrandar a metodologia de erradicação significa comprometer esse elevado nível de sanidade dos pomares e a competitividade da citricultura, com reflexos negativos financeiros e ambientais. Diante desses fatos sugere-se: a) que a erradicação da doença volte a ser feita como anteriormente utilizada; ou b) a adoção de uma nova metodologia de erradicação, mais efetiva na supressão da doença, quando em novos levantamentos amostrais de cancro cítrico em São Paulo forem encontradas incidências de talhões comerciais com a doença superiores a 0,36%. Essa incidência foi calculada comparando-se pelo teste de Duncan (P<0,05) os levantamentos amostrais de cancro cítrico realizados de 1999 a 2009. A diferença mínima significativa encontrada foi de 0,28. A menor incidência do cancro cítrico em São Paulo foi de 0,08%, observada em 2001. Dessa forma, como alternativa, propõe-se a adoção de uma metodologia mais drástica de erradicação do cancro cítrico quando em um novo levantamento amostral for detectado mais que 0,36% de talhões comerciais com cancro cítrico.

Identificação de genes cry de Bacillus thuringiensis no controle de Sphenophorus levis, o bicudo da cana-de-açúcar

A bactéria B. thuringiensis caracteriza-se pela produção de proteínas tóxicas a representantes de diversas ordens de insetos, as quais são codificadas por genes cry. Este trabalho foi realizado com objetivo de selecionar isolados de B. thuringiensis, por meio da caracterização morfológica e molecular, identificando as diferentes subclasses dos genes cry3 e cry35 e determinar a patogenicidade contra Sphenophorus levis, uma das mais importantes pragas da cultura da cana-de-açúcar. Foram utilizados 1163 isolados de B. thuringiensis e com a observação em microscópio com contraste de fases foram confirmadas como pertencentes à espécie de B. thuringiensis. O material genético foi purificado pela matriz de troca iônica Instagene Matrix e submetido a PCR com iniciadores gerais cry3 e cry35 identificando-se 30 isolados contendo genes com potencial para o controle de coleópteros, os quais juntamente com as linhagens-padrão de B. thuringiensis var. tenebrionis, B. thuringiensis var. morrissone e B. thuringiensis var. tolworthi foram utilizados para a realização do bioensaio. Através de análise discriminante alocaram-se os isolados em quatro grupos quanto à toxicidade de B. thuringiensis. Os grupos ficaram assim definidos: um grupo que promovem até 10% de mortalidade contendo as testemunhas e duas linhagens;um grupo que causou 39% de mortalidade contendo três linhagens padrão e dez isolados; um grupo com 52% de mortalidade contendo treze isolados e um grupo com 70% de mortalidade contendo cinco isolados, os quais devem ser considerados promissores no controle biológico de S. levis.