Tretinoin-based formulations - influence of concentration and vehicles on skin penetration

A tretinoína é usada no tratamento de acne e é considerada como padrão de ouro para o tratamento do fotoenvelhecimento. Em altas concentrações, é relatada como um agente para peeling químico superficial, com poucas considerações sobre a penetração na pele. O objetivo deste estudo foi avaliar a influência da concentração do fármaco e os veículos comumente usados na penetração cutânea da tretinoína. Testes in vitro de penetração foram realizados com células de difusão de Franz equipados com pele da orelha de porco e 10% de solução aquosa de metanol no compartimento receptor. As formulações estudadas, creme ou dispersão hidroalcoólica, contendo 0,25%, 1% e 5% de tretinoína foram colocadas no compartimento doador, durante seis horas. A concentração da tretinoína foi medida por cromatografia líquida de alta eficiência. A maior quantidade de tretinoína foi detectada no estrato córneo com diferenças significativas entre as três concentrações. A dispersão hidroalcoólica foi o melhor veículo. Quantidades significativas de tretinoína foram encontradas nas camadas profundas da epiderme. A formulação com 0,25% de tretinoína mostrou melhores resultados em termos de porcentagem penetrada na pele. Por fim, a penetração de tretinoína na pele foi influenciada pelo veículo e pela concentração desta utilizada na formulação.Tretinoin is used in the management of acne and it is part of a gold standard treatment for photoaging. It has also been reported as an agent for superficial chemical peeling in highly concentrated formulations with few considerations about skin penetration. The aim of this study was to evaluate the influence of drug concentration and vehicles currently used on skin penetration of tretinoin. In vitro permeation tests were carried out using Franz diffusion cells fitted with porcine ear skin and 10% aqueous methanol in the receptor compartment. Formulations studied, cream or hydroalcoholic dispersion, containing 0.25%, 1% and 5% of tretinoin were placed in the donor compartment for six hours. Tretinoin concentration in skin layers was measured by high performance liquid chromatography. The largest amount of tretinoin from both vehicles was detected in stratum corneum with significant differences among the three concentrations. The hydroalcoholic dispersion was the best vehicle. Significant amounts of tretinoin were found even in deep layers of epidermis. The formulation with 0.25% tretinoin showed better results when considered the amount of tretinoin on skin in terms of percentage. Finally, skin penetration of tretinoin was influenced by vehicle and concentration of this drug used in formulation

Benefits of Combinations of Vitamin A, C and E Derivatives in the Stability of Cosmetic Formulations

Chemically stable ester derivatives of vitamins A, C and E have become a focus of interest for their role in the satisfactory results in skin aging treatments. Accordingly, the aim of this study was to evaluate the physical and chemical stability of a cosmetic formulation containing 1% retinyl palmitate, ascorbyl tetraisopalmitate and tocopheryl acetate, alone or in combination. In the studies of physical stability, a Brookfield rheometer was used to determine rheological behavior of formulations containing the vitamins. Chemical stability was determined by HPLC on a Shimadzu system with UV detection. Results showed that formulations had pseudoplastic behavior and that vitamins did not alter their apparent viscosity and thixotropy. In the chemical stability studies, first-order reaction equations were used for determinations of the shelf-life of vitamins derivatives considering a remaining concentration of 85%. Combined vitamins in a single formulation had a slightly lower degradation rate as compared to different preparations containing only one of the vitamins. Considering that many cosmetic formulations contain vitamin combinations it is suggested that the present study may contribute to the development of more stable formulations containing liposoluble vitamins.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Research Pro-Rectory-University of Sao Paul

Tretinoin-based formulations - influence of concentration and vehicles on skin penetration

Tretinoin is used in the management of acne and it is part of a gold standard treatment for photoaging. It has also been reported as an agent for superficial chemical peeling in highly concentrated formulations with few considerations about skin penetration. The aim of this study was to evaluate the influence of drug concentration and vehicles currently used on skin penetration of tretinoin. In vitro permeation tests were carried out using Franz diffusion cells fitted with porcine ear skin and 10% aqueous methanol in the receptor compartment. Formulations studied, cream or hydroalcoholic dispersion, containing 0.25%, 1% and 5% of tretinoin were placed in the donor compartment for six hours. Tretinoin concentration in skin layers was measured by high performance liquid chromatography. The largest amount of tretinoin from both vehicles was detected in stratum corneum with significant differences among the three concentrations. The hydroalcoholic dispersion was the best vehicle. Significant amounts of tretinoin were found even in deep layers of epidermis. The formulation with 0.25% tretinoin showed better results when considered the amount of tretinoin on skin in terms of percentage. Finally, skin penetration of tretinoin was influenced by vehicle and concentration of this drug used in formulation

Stability and clinical efficacy of dermocosmetic formulations containing UV filters, liposoluble vitamins and Ginkgo biloba and red alga extracts

A associação de substâncias ativas no desenvolvimento de produtos multifuncionais eficazes para a manutenção e restauração da integridade da pele têm sido imprescindível na área cosmética. Desta maneira, destaca-se a associação de filtros solares com substâncias antioxidantes, tais como as vitaminas lipossolúveis e os extratos vegetais, com propriedades de filtros solares biológicos, os quais podem fornecer benefícios únicos à pele, aumentando a proteção contra a radiação UV e melhorando suas condições e aspectos em geral. Ainda, no desenvolvimento de formulações cosméticas é fundamental a seleção rigorosa e o balanço adequado de matérias-primas para a obtenção de produtos seguros, eficazes e estáveis durante todo seu tempo de prateleira. Assim, o objetivo do presente projeto é a avaliação da estabilidade física e química e da eficácia clínica de formulações dermocosméticas contendo filtros solares, vitaminas lipossolúveis e extratos de Ginkgo biloba e de algas marinhas vermelhas. Para tal, foram desenvolvidas 11 formulações fotoprotetoras as quais foram acrescidas ou não dos extratos de Ginkgo biloba ou de algas marinhas vermelhas e/ou de uma associação de vitaminas lipossolúveis. Após a realização de testes preliminares de estabilidade, as formulações F11, F11X e F11N (á base de poliacrilamida, C13-14 isoparafina e lauret-7) não apresentaram sinais de instabilidade e, portanto, foram submetidas à avaliação da estabilidade física (reologia). As formulações F11X e F11N foram consideradas mais estáveis, uma vez que não apresentaram grandes variações nos parâmetros analisados durante o estudo reológico (viscosidade aparente mínima, índice de fluxo, índice de consistência e área de histerese) e foram então utilizadas nos estudos posteriores. No estudo de estabilidade química as formulações contendo as diferentes substâncias ativas apresentaram diferentes prazos de validades, sendo que para a formulação que continha a associação de extratos e vitaminas (F11XVGA), o prazo de validade foi considerado maior quando comparado com as formulações que continham estas substâncias isoladas. Na avaliação da compatibilidade cutânea nenhum sinal clínico ou sensação de desconforto foi observado. No estudo de quantificação do limiar de percepção a uma corrente elétrica a formulação contendo associação de vitaminas e extratos vegetais de Ginkgo biloba e algas marinhas vermelhas proporcionou um aumentou a sensibilidade das fibras Ab devido a um aumento da hidratação, o que é essencial para manter as condições de percepção da pele. Na avaliação do efeito protetor contra as variações do clima a formulação F1XVGA apresentou efeito significativo benéfico na sensação de hidratação da pele e uma tendência em melhorar a sensibilidade das fibras nervosas C e Ad. Após uma única aplicação formulação estudada aumentou o conteúdo aquoso do estrato córneo, mostrando, portanto, efeito hidratante na pele, e ainda protegeu a função barreira da pele. No estudo de eficácia clínica a a formulação multifuncional proposta proporcionou uma melhora na função barreira da pele e uma hidratação que atinge até as camadas mais profundas da epiderme, levando a uma melhora na aparência da pele pela diminuição de rugas e da aspereza cutânea, podendo ser proposta para prevenir e melhorar as condições da pele foto envelhecida.The association of active substances in the development of multifunctional cosmetic products, to be effective for the maintenance and restoration of skin integrity, have been essential in cosmetic area. Thus, a combination of sunscreen with antioxidant substances, such as liposoluble vitamins derivatives and vegetable extracts may provide unique benefits to the skin, increasing their protection against UV radiation and improving their conditions and appearance. Further, in the development of cosmetic formulations it is essential to assure the selection and balance of raw materials desirable for obtaining safe, efface and stable cosmetic formulations. The objective of this study is to evaluate the physical and chemical stability and clinical efficacy of dermocosmetic formulations containing sunscreens, liposoluble vitamins and Ginkgo biloba and red sea algae extracts For this, formulations it were developed 11sunscrrens which were added or not with vegetables extracts of Ginkgo biloba or from red sea algae and / or a combination of liposoluble vitamins derivatives. After conducting preliminary stability tests, formulations F11, F11X and F11N (based on polyacrylamide, C13-14 isoparaffin and laureth-7) showed no signs of instability and therefore were evaluated for physical stability (rheology). The formulations F11X and F11N were considered more stable, since they do not show variations in the parameters examined during the rheology study (viscosity, flow index, and consistency index, and tixotrophy) and were then used in further studies. In the chemical stability study formulations containing different active substances showed different shelf lives, and the formulation containing the combination of active substances (F11XVGA), the shelf life was considered higher when compared with formulations containing these substances alone. In the assessment of skin compatibility no clinical signs or discomfort was observed. In the current perception threshold study the formulation containing the combination of vitamins and vegetable extracts increased sensitivity of the Ab fibers due to increased hydration, which is essential for maintaining conditions of skin perception. In the evaluations of the protective effect against the environments variations the formulation F1XVGA was effective on the beneficial feeling of hydration of the skin and a tendency to improve the sensitivity of nerve fibers C and Ad. After a single application, the studied formulation increased the water content of the stratum corneum, showing therefore moisturizing effect on the skin, and also protected the skin barrier function. In clinical efficacy study the multifunctional proposed formulation provided an improvement in skin barrier function and hydrations until the deeper layers of the epidermis, leading to an improvement in skin appearance by reducing wrinkles and skin roughness, which can be suggest preventing and improving skin conditions mainly related with photo aging