EMULGEL BASEADO EM QUITOSANA CONTENDO EXTRATO DE PRÓPOLIS VERMELHA PARA TRATAMENTO DE INFECÇÕES VULVOVAGINAIS

As abelhas coletam um produto natural resinoso a partir da planta Dalbergia ecastophyllum, uma espécie nativa de manguezais brasileiros do estado de Alagoas, que origina a própolis vermelha. Neste trabalho, prepararam-se diferentes extratos da própolis vermelha para desenvolver uma formulação tópica para tratamento de infecções vulvovaginais, como vaginoses bacterianas e candidíase. Ensaios de atividade antimicrobiana dos extratos frente aos microrganismos de referência Candida albicans ATCC 90028, Staphylococcus aureus ATCC 25923 e Escherichia coli ATCC 25922 indicaram que o extrato preparado em polietilenoglicol 400 apresentou notável atividade antimicrobiana contra C. albicans e S. aureus. Prepararam-se formulações com baixo teor de componentes oleosos, do tipo emulgel, com incorporação do extrato que apresentou maior atividade antimicrobiana. A mistura de uma emulsão não iônica com um hidrogel de quitosana de baixo peso molecular na proporção 1:1 p/p originou o emulgel. Caracterizaram-se as propriedades reológicas da emulsão, do gel de quitosana e do emulgel. A incorporação do extrato no emulgel contendo quitosana resultou em uma atividade antimicrobiana in vitro aumentada, como uma alternativa terapêutica viável baseada em produtos naturais para tratamento de infecções vulvovaginais. A realização de estudos clínicos ainda se faz necessária para caracterizar a segurança e eficácia destas formulações

Evaluation of skin absorption of drugs from topical and transdermal formulations

The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed

In vitro evaluation of transdermal nicotine delivery systems commercially available in Brazil

The aim of this study was to develop and validate a method for evaluating the release and skin permeation from transdermal nicotine patches using the vertical diffusion cell (VDC). The VDC is an experimental apparatus employed in research, development, and the pharmaceutical field because it can simulate conditions closest to those established in clinical trials. Two transdermal nicotine delivery systems marketed in Brazil to release 14 mg over 24 hours were evaluated. Release studies were carried out using a regenerated cellulose dialysis membrane and permeation studies were carried out using excised porcine ear skin. The results indicated that nicotine release from both evaluated patches follows Higuchi's release kinetics, while skin permeation studies indicated zero-order release kinetics. Nicotine release rates were different between both evaluated patches, but drug permeation rates were not significantly different. According to validation studies, the method was appropriate for evaluating in vitro performance of nicotine patches. The proposed method can be applied to in vitro comparative studies between different commercial nicotine patches and may be used as an auxiliary tool in the design of new transdermal nicotine delivery systems.O objetivo deste trabalho foi o desenvolvimento e a validação de metodologia empregando a célula de difusão vertical para avaliação da liberação e permeação cutânea in vitro de nicotina a partir de adesivos transdérmicos. A célula de difusão vertical é considerada um aparato experimental importante em pesquisa e desenvolvimento e pode simular condições in vitro próximas aquelas observadas em ensaios clínicos. Neste trabalho foram avaliados dois dispositivos transdérmicos comercializados no Brasil para liberação controlada de 14 mg de nicotina em um período de 24 horas. Realizaram-se ensaios de liberação, usando membranas de diálise de celulose regenerada, e estudos de permeação cutânea, usando pele de orelha de porcos. Os resultados indicaram que a liberação da nicotina em ambos os dispositivos transdérmicos avaliados seguiu a cinética de Higuchi, enquanto que a permeação cutânea seguiu cinética de ordem zero. As velocidades de liberação foram diferentes para os dispositivos comerciais avaliados, entretanto não foram encontradas diferenças significativas para as velocidades de permeação cutânea. Conforme os estudos de validação, a metodologia mostrou-se apropriada para a avaliação in vitro da liberação e permeação cutânea a partir de adesivos transdérmicos de nicotina. O método proposto foi aplicado em estudos comparativos in vitro entre adesivos transdérmicos comerciais contendo nicotina. Deste modo, o método também pôde ser considerado como ferramenta útil que poderia ser aplicada durante o desenvolvimento de novas formulações transdérmicas para liberação de nicotina

Analysis of spironolactone polymorphs in active pharmaceutical ingredients and their effect on tablet dissolution profiles

Spironolactone (SPR) is a steroidal drug administered as a potassium-sparing diuretic for high blood pressure treatment. The drug shows incomplete gastrointestinal absorption due to its poor aqueous solubility. The physicochemical properties of SPR in crystal forms I and II suggest that differences in their aqueous solubility may lead to a lack of bioequivalence between solid-state formulations. In this study, SPR polymorphs in five batches of active pharmaceutical ingredients (APIs) from three manufacturers were characterized using powder X-ray diffraction, infrared spectroscopy, thermal analysis, and solubility measurements. SPR tablets (50 mg) were manufactured in our laboratory using API in pure form II, and API in form II contaminated with form I, which was found in a commercial batch. Physicochemical quality evaluations of the manufactured tablets, along with five SPR tablets marketed in Brazil, were performed, and results indicated differences in their dissolution profiles. In the manufactured tablets, differences were associated with the increased solubility of API in form II contaminated with form I compared to API in pure form II. In the marketed SPR tablets, the formulation composition demonstrated an important role in the dissolution rate of the drug, leading to lack of pharmaceutical equivalence among the drug products

DESENVOLVIMENTO E CARACTERIZAÇÃO QUÍMICA DE FRAGRÂNCIAS A PARTIR DE ÓLEOS ESSENCIAIS E FLAVORIZANTE SINTÉTICO

Os perfumistas elaboram composições de fragrância a partir de matérias-primas odoríferas. Os perfumes recebem classificações conforme a concentração da fragrância nas suas formulações, como parfums (entre 15 e 30% de fragrância); eau de parfums (8 a 15% de fragrância); eau de toilettes (4 a 15% de fragrância) e os eau de colognes (3 a 5% de fragrância). O presente trabalho teve como objetivo desenvolver e caracterizar uma fragrância, e incorporá-la em um produto cosmético para uso em perfumaria. O desenvolvimento da fragrância foi baseado em 21 combinações de compostos aromáticos obtidos comercialmente ou preparados por hidrodestilação em Clevenger, incluindo ou não um aromatizante sintético. A fragrância selecionada continha uma mistura dos óleos essenciais (Pogostemon cablin, Amyris balsamifera, Citrus limon e Baccharis dracunculifolia) combinados a essência sintética de maracujá. A formulação de perfume definida consistiu em 7% da fragrância selecionada, etanol como veículo, propilenoglicol como umectante, triclosan como conservante e galaxolide como fixador. A técnica cromatografia gasosa acoplada a espectrometria de massas permitiu a caracterização química do perfume. A determinação do índice de retenção e comparação com a literatura e banco de dados da biblioteca Wiley permitiu a identificação das substâncias voláteis na formulação. Os principais constituintes voláteis determinados no perfume foram valerianol (12,5%), limoneno (6,7%) e β-cariofileno (6,7%). Foi possível demonstrar o potencial de fontes naturais, especialmente aquelas oriundos da biodiversidade brasileira, para produção de compostos aromáticos a partir destes resultados

Evaluating the discriminatory power of a dissolution assay for rosuvastatin calcium capsules: Solid-state properties and dissolution media

We propose to evaluate the dissolution properties of rosuvastatin calcium (ROSC) capsules in different media to characterize the discriminatory power of the assay method. Dissolution assays were performed in media with different pH, and including the surfactant sodium dodecyl sulfate (SDS). Several immediaterelease formulations were manufactured using the commercial raw material characterized as amorphous solid. The hydrophobic adjutant magnesium stearate was employed in some formulations due to its negative effect in the wettability and dissolution efficacy of solid dosages. These formulations showed the lower dissolution efficacy values in media without surfactant; however, when SDS was added to the medium, the dissolution efficacy increased, and the discriminatory power was lost. In spite of micellar solubilization does not increase the ROSC solubility, it modifies the discriminatory power of the assay method, increasing the wettability of the powder mixtures. The crystalline form M of ROSC was recrystallized in our laboratory, and it showed lower solubility in water than amorphous solid. However, its dissolution properties were not influenced by SDS. These results are important to develop dissolution assays for other hydrophilic drugs with increased water solubility, once that dissolution media with surfactants increase the wettability of the formulations, leading to an overrated dissolution rate

In vitro evaluation of transdermal nicotine delivery systems commercially available in Brazil

The aim of this study was to develop and validate a method for evaluating the release and skin permeation from transdermal nicotine patches using the vertical diffusion cell (VDC). The VDC is an experimental apparatus employed in research, development, and the pharmaceutical field because it can simulate conditions closest to those established in clinical trials. Two transdermal nicotine delivery systems marketed in Brazil to release 14 mg over 24 hours were evaluated. Release studies were carried out using a regenerated cellulose dialysis membrane and permeation studies were carried out using excised porcine ear skin. The results indicated that nicotine release from both evaluated patches follows Higuchi's release kinetics, while skin permeation studies indicated zero-order release kinetics. Nicotine release rates were different between both evaluated patches, but drug permeation rates were not significantly different. According to validation studies, the method was appropriate for evaluating in vitro performance of nicotine patches. The proposed method can be applied to in vitro comparative studies between different commercial nicotine patches and may be used as an auxiliary tool in the design of new transdermal nicotine delivery systems

Evaluation of skin absorption of drugs from topical and transdermal formulations

ABSTRACT The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed

Desenvolvimento e validação de um método analítico rápido por cromatografia líquida de alta eficiência para determinação de nimesulida em estudos de liberação in vitro

A high performance liquid chromatography (HPLC) method has been developed for a rapid determination of nimesulide in dissolution studies. Nimesulide was analyzed using 5 µm Lichrospher® RP-18 column (125 x 4 mm i.d.) and mobile phase acetonitrile: phosphate buffer pH=6.0 (55:45) at a flow-rate of 1.0 mL min-1. Detection was carried out at 300 nm at 25 ºC. The method was applied to analysis of nimesulide in in vitro release studies and showed a rapid and efficient analytical alternative for evaluation of dissolution profile of nimesulide