Currently, medications used in children are typically modified from pharmaceutical dosage forms designed for adults. Captopril is widely adapted to liquid formulations for use in hospitals. Its stability in the aqueous medium is reduced since it undergoes oxidation producing captopril disulfide (its main metabolite). The aim of this formulation study was to suggest favorable conditions for the development of a stable captopril formulation. The compatibility between the drug and excipients was evaluated by differential scanning calorimetry analysis (DSC). For studies in solution, different formulations were prepared according to a factorial design varying EDTA concentration, water purity and pH. The resultant formulations were stored at 60°C and analyzed over a twelve-day period using HPLC. The DSC curves obtained suggested, although not conclusive to elucidation, interactions of captopril with citric acid and sucralose. The stability study of these solutions revealed that the variables significantly influenced captopril content, which degraded at zero order kinetics and rates differing by a factor of up to 7 times, where pH proved the most influential factor. Interactions between variables were observed. Therefore, development of a stable captopril formulation is feasible provided EDTA and a buffering agent is used at suitable concentrations (0.08% and pH 3.85).

ABSTRACTCissampelos sympodialis Eichler, Menispermaceae, is widely used by Indian tribes and folk medicine to treat various inflammatory disorders, including asthma. Clinical toxicological trials were made with the tea of C. sympodialis, a medicinal plant. The study took place at Lauro Wanderley Hospital/UFPB-PB, where seventeen healthy volunteers were chosen, among those six men and eleven women who orally ingested, during four weeks uninterruptedly, 150 ml of the tea, once a day. Before the first ingestion and after the last one, the participants were subjected to clinical and laboratorial tests for their overall conditions in order to analyze the toxicity of the plant. The results demonstrated that the volunteers neither experience clinical nor laboratorial alterations, as well as no significant adverse effects, apart from little change detected in their hematological tests. Nevertheless, none demonstrated any pathological conditions, just alterations of the normal human being physiology. Therefore, it is concluded that these data complement that obtained during pre-clinical studies and confirm a low toxicity of this plant.

Isoniazida e rifampicina são fármacos de primeira escolha para a prevenção e tratamento da tuberculose. A rifampicina degrada-se em condições ácidas do estômago, principalmente na presença da isoniazida, o que contribui para a falha do tratamento. O presente trabalho teve como objetivo a obtenção de péletes de isoniazida gastrorresistentes, visando a evitar contato da rifampicina com isoniazida e consequente degradação no meio ácido estomacal. Os péletes foram produzidos pela técnica de extrusão-esferonização. O processo de revestimento foi conduzido em leito fluidizado com solução orgânica de Acrycoat L 100(r). Os péletes obtidos foram submetidos ao teste de dissolução em HCl 0,1 N e tampão fosfato. Os resultados indicam que a gastrorresistência foi obtida somente com a maior quantidade de revestimento, sendo a isoniazida liberada completamente no meio tampão fosfato. A quantidade de rifampicina dissolvida em meio ácido, quando associada a péletes de isoniazida não revestidos, foi menor do que a observada na presença de péletes de liberação entérica. O polímero Acrycoat L 100(r) mostrou-se eficiente para o recobrimento com a função de gastrorresistência, indicando que a instabilidade da rifampicina pode ser reduzida nas associações com a isoniazida através do revestimento entérico da isoniazida.

Isoniazid and rifampicin are considered the first-line medication for preventing and treating tuberculosis. Rifampicin is degraded in the stomach acidic environment, especially when combined with isoniazid, factor contributing to treatment failure. In this study, gastric-resistant isoniazid pellets were obtained to physical contact of this drug with rifampicin and to bypass the stomach´s acidic environment. The pellets were fabricated using the extrusion-spheronization technique. The coating process was conducted in a fluid spray coater using Acrycoat L 100(r) solution as the coating agent. The pellets obtained were submitted to a dissolution test in HCl 0.1 N and phosphate buffer media. The results indicated that optimum gastric-resistance was only attained with the highest amount of coating material, with isoniazid almost fully released in phosphate buffer. The amount of rifampicin released from its mixture with non-coated isoniazid pellets in HCl 0.1 N was less than that released from its mixture with the enteric-coated pellets. Acrycoat L 100(r) was shown to be an effective enteric/gastric-resistant coating since the stability of rifampicin appeared to be enhanced when physical contact of this drug with isoniazid was prevented at low pH.

Euterpe oleracea Mart. é uma palmeira popularmente conhecida como açaí, encontrada no norte do Brasil. O fruto do açaí apresenta em sua composição antocianinas, uma classe de polifenóis à qual é atribuída propriedade antioxidante. Os objetivos desse trabalho foram desenvolver emulsões fotoprotetoras O/A contendo extrato glicólico de açaí (AGE), avaliar a estabilidade física e avaliar a eficácia fotoprotetora. Emulsões contendo AGE e filtros solares foram formuladas utilizando diferentes tipos e concentrações de tensoativo polimérico (acrilates/C 10-30 alquil acrilato polímero cruzado e polilacrilato sódico). A influência de dois modificadores reológicos (poliacrilamida (e) C13-14/isoparafina (e) Laureth-7 e Carbomer) na estabilidade foi avaliada. A estabilidade física das emulsões foi avaliada por meio de estudos de estabilidade preliminar e acelerada. Emulsões com 1,0% poliacrilato sódico foram estáveis, exibiram comportamento não-newtoniano pseudoplástico e tixotrópico. A eficácia fotoprotetora foi avaliada pelo teste in vivode Fator de Proteção Solar (FPS) e pela determinação do Fator de Proteção UVA (FP-UVA). Quando adicionado o AGE na emulsão contendo filtros solares, não se observou aumento significativo no valor do FPS. A emulsão contendo o AGE apresentou FP-UVA=14,97, a razão FPS/FP-UVA = 1,69 e o comprimento de onda crítico igual a 378 nm, podendo ser considerado um protetor solar com proteção UVA e UVB.

Euterpe oleraceaMart. is a palm tree popularly known as açai, which is primarily found in northern Brazil. The açai's fruits contain anthocyanins, a class of polyphenols to which antioxidant properties have been attributed. The aim of this work was to develop O/W sunscreens emulsions containing açai glycolic extract (AGE) and to evaluate both their physical stability and photoprotective efficacy. Emulsions containing AGE and sunscreens were formulated using different types and concentrations of polymeric surfactant (acrylates/C 10-30 alkyl acrylate crosspolymer and sodium polyacrylate). The influence of two rheology modifiers (polyacrylamide (and) C13-14/isoparaffin (and) Laureth-7 and Carbomer) on the stability was also investigated. Physical stability was evaluated by preliminary and accelerated studies. Emulsions with 1.0% sodium polyacrylate were stable and exhibited non-newtonian pseudoplastic behavior and thixotropy. Photoprotective efficacy was evaluated by in vivo Sun Protection Factor (SPF) and determination of Protection Factor of UVA (PF-UVA). When AGE was added to the sunscreen emulsion, no significant increase in the in vivo SPF value was observed. The emulsion containing AGE showed PF-UVA = 14.97, 1.69 of the SPF/PF-UVA ratio and a critical wavelength value of 378 nm, and may therefore be considered a sunscreen with UVA and UVB protection.

O presente estudo teve como objetivo a otimização de parâmetros cinéticos de extração da Cinchona pubescens Vahl por ultra-som, usando métodos farmacopéicos e não farmacopéicos. Na extração por ultrasom variaram-se o tempo, a massa, a faixa granulométrica, o volume de solvente e o tipo de solvente. Na decocção, as extrações foram feitas no tempo e temperatura descrita na Farmacopéia Brasileira IV, variando-se o sistema solvente. Na extração por maceração variaram-se o tempo e o sistema solvente. O teor de alcalóides quinolínicos foi monitorado por espectrofotometria no UV a 325 nm. O método decocção foi o que apresentou o maior rendimento na extração dos alcalóides, dados equivalentes foram conseguidos com o método ultra-som, no tempo de 5 min e solvente acidificado pH 4, com um rendimento maior ao da maceração. Pela aplicação do planejamento fatorial para o método do ultra-som foi visto que há uma interação entre as variáveis, necessitando de um melhor ajuste entre elas a fim de melhorar a eficiência extrativa do método do ultra-som.

The present study for ultrasound had as objective the optimization of kinetic parameters of extraction of the Cinchona pubescens Vahl, using pharmacopeia and no pharmacopeia methods. In the extraction for ultrasound they had varied the time, the solvent type, the mass, the volume of solvent and grain size of the sample. In the decoction, the extractions had been made according to the time and temperature described in Brazilian Pharmacopeia IV, varying the solvent system. In the extraction for maceration the time and the solvent system had varied. The alkali of the Cinchona pubescens Vahl, was monitored by spectrophotometry in UV 325 nm. The method decoction was the one that presented the biggest income in the alkaloids extraction, given equivalent data had been obtained with the method ultrasound, in the solvent acidified pH 4 and time of 5 min, with a bigger income than the one of the maceration.

O presente trabalho se propõe avaliar a atividade citotóxica do extrato etanólico bruto e da fração dos alcalóides totais (FAT) da planta Crotalaria retusa para células promastigotas metacíclicas de Leishmania chagasi. O estudo da cinética de extração por ultra-som para os alcalóides totais da Crotalaria retusa, tornou possível a otimização dos parâmetros de extração. Foi avaliada a ação leishmanicida da FAT da planta em estudo, a qual não mostrou atividade citotóxica em altas concentrações. Foi observado uma potente ação leishmanicida para os extratos etanólicos (10 e 30%) após a concentração de 5,6 mg/mL de Crotalaria retusa e do etanol presente na solução extrativa (10 e 30%) nas concentrações de 70 e 210 x 10-4 %, respectivamente. Estes resultados sugerem a citotoxicidade do extrato etanólico da Crotalaria retusa de 10 a 30% para células de Leishmania chagasi, associada possivelmente à concentração do etanol presente no extrato.

The purpose of the present work is to conduct an evaluation of the cytotoxicity of ethanol extracts and the total alkaloid fraction (TAF) from Crotalaria retusa for procyclic promastigotes cells of Leishmania chagasi. The kinetic study of extraction assisted by ultrasound of the total alkaloids present in Crotalaria retusa made it possible the optimization of the extraction parameters. It was evaluated the leishmanicide action of the TAF which did not show toxic activity for cells of the parasite in high concentrations. It was observed a powerful leishmanicide action of the ethanol extracts (10 and 30%) after the concentration of 5.6 mg/mL of Crotalaria retusa, and the ethanol present in the extractive solution (10 and 30%) in the concentration from 70 and 210 x 10-4 %, respectively. These results suggest that the cytotoxicity of the ethanol extract of Crotalaria retusa at 10 and 30% for cells of Leishmania chagasi, can be associated only to the concentration of the alcohol present in the extract.

Já está bem estabelecido na literatura científica que produtos naturais ou sintéticos podem alterar a biodistribuição de radiofármacos. O objetivo desse estudo foi avaliar a influência do paclitaxel, um agente antineoplásico para tratamento de tumores sólidos na biodistribuição do pertecnetato de sódio em ratas Wistar e na determinação de componentes bioquímicos e hematológicos. Paclitaxel, comercialmente conhecido por Taxol® (1mg/mL/semana), foi administrado, intraperitoneamente, nos animais do grupo tratado, em dose única, por 3 semanas, mas com intervalo de uma semana entre elas. O grupo controle recebeu solução de NaCl 0,9%. Uma hora após a última dose de paclitaxel, os animais receberam 0,1 mL de Na99mTcO4 (3,7MBq) via plexo orbital. O percentual de radioatividade por grama (%ATI/g) e parâmetros laboratoriais foram determinados. Ocorreu um aumento significativo (p<0,05) do %ATI/g nos ovários, útero, vagina, mamas, intestino grosso e fígado. Os níveis de glicose sangüínea e das enzimas hepáticas (ALT e AST) também aumentaram significantemente (p<0,01). Esses resultados podem estar associados, provavelmente, à capacidade do paclitaxel em alterar a biodistribuição do Na99mTcO4 e o metabolismo da glicose e de enzimas hepáticas.

The evidence that natural or synthetic drugs can affect the biodistribution of radiopharmaceuticals (radiobiocomplexes) in setting of nuclear medicine clinic is already known. We studied the effect of Paclitaxel, an anti-neoplastic agent for the treatment of solid tumors, on the biodistribution of Na99mTcO4 in female rats. Paclitaxel (1mg/mL/week) was administered into animals in single dose during 3 weeks, with interval of 1 week among them. The control group received NaCl 0.9% solutions by the same via. One hour after the last dose, it was injected Na99mTcO4 in the animals. The percentage of activity per gram (%ATI/g) and biochemical and hematological determinations were performed. A significant increase were found in alanine aminotransferase, aspartate aminotransferase, glucose and in the %ATI/g of some organs (ovaries, uterus, vagina, breasts, large intestine and liver).These results can be associated, probably, to the capacity of paclitaxel to alter the biodistribution of Na99mTcO4 and the metabolism of glucose and hepatic enzymes.