RESUMEN

O objetivo desse estudo foi analisar o perfil de liberação do princípio ativo peróxido de hidrogênio por diferentes géis clareadores no decorrer do período de aplicação. Para tal diferentes géis clareadores à base de peróxido de hidrogênio para uso na técnica em consultório foram levados à câmara doadora de uma célula de difusão vertical (célula Franz). Foi empregado como meio de difusão uma membrana de éster de celulose com porosidade de 100-500 Daltons. A câmara receptora foi preenchida com água ultrapura. Os seguintes géis foram testados: Whiteness HP (FGM), Whiteness HP Blue (FGM), Whiteness HP Automix (FGM), Potenza Bianco (PHS do Brasil), Opalescence Boost (Ultradent), e Pola Office Plus (SDI); solução de peróxido 35% controle. O peróxido de hidrogênio liberado pelo gel se difundiu através da membrana e se misturou com a água na câmara receptora. Uma amostra de 40µl foi coletada da câmara receptora a cada 5 min, durante 45 minutos e foi reposto o mesmo volume de 40 µl em água ultrapura. A concentração de peróxido na amostra (mg/ml) foi determinada em triplicata a cada momento, utilizando um espectrofotômetro leitor de microplacas e reagente enzimático. A normalidade e homoscedasticidade dos dados foram avaliadas pelos testes de Shapiro-Wilk e Levene. Os dados de quantidade acumulada de peróxido foram submetidos ao teste de análise de variância ANOVA a 2 fatores (tipo de gel x tempo) e teste de Tukey. Para todas as análises foi adotado um nível de significância de 5%. Diferenças significativas foram observadas para os fatores agente clareador (p=0,0001) e tempo (p=0,0001), assim como para a interação entre eles (p=0,0001). Os resultados do teste de Tukey para o fator agente clareador quanto à quantidade cumulativa de peróxido foram: WHPB-14,04(6,60)a, WHP19,51(8,61)b, WHPA-23,20(10,48)c, POP-26,53(11,13)d, PB-28,29(10,99)de, OPB31,03(11,81)e, Controle 79,12(32,27)f. Para o fator tempo, em minutos, os resultados foram: 5 9,64(6,70)a, 10-17,42(11,60)b, 15-24,03(16,86)c, 20-29,50(20,44)d, 25-33,93(23,00)e, 30-38,41(25,83)f, 35-41,52(27,32)fg, 40-44,11(28,47)gh, 45- 46,50(29,72)h. Os resultados do teste ANOVA de medidas repetidas mostraram diferenças significativas (p=0,00) em relação a concentração inicial e final de peróxido para os fatores agente clareador, momento de leitura e para a interação entre eles. Agentes clareadores com maior concentração inicial de peróxido de hidrogênio apresentaram maior liberação cumulativa do ingrediente ativo; a liberação de peróxido de hidrogênio de diferentes géis clareadores ocorre de maneira gradual em relação ao tempo de aplicação, porém essa liberação não ocorre de maneira constante.(AU)

The aim of this study was to analyze the release profile of the active ingredient hydrogen peroxide by different bleaching gels over the course of the application period. For this purpose, different bleaching gels based on hydrogen peroxide for use in the in-office technique were taken to the donor chamber of a vertical diffusion cell (Franz cell). A cellulose ester membrane with a porosity of 100-500 Daltons was used as diffusion medium. The receiving chamber was filled with ultrapure water. The following gels were tested: Whiteness HP (FGM), Whiteness HP Blue (FGM), Whiteness HP Automix (FGM), Potenza Bianco (PHS do Brasil), Opalescence Boost (Ultradent), and Pola Office Plus (SDI); 35% peroxide control solution. The hydrogen peroxide released by the gel diffused through the membrane and mixed with the water in the receiving chamber. A 40µl sample was collected from the receiving chamber every 5 min for 45 minutes and the same volume of 40 µl was replaced in ultrapure water. The peroxide concentration in the sample (mg/ml) was determined in triplicate at each time point, using a microplate reader spectrophotometer and enzymatic reagent. Data normality and homoscedasticity were evaluated using the Shapiro-Wilk and Levene tests. Accumulated amount of peroxide data was submitted to 2-way ANOVA test of variance (type of gel x time) and Tukey's test. For all analyses, a significance level of 5% was adopted. Significant differences were observed for the factors bleaching agent (p=0.0001) and time (p=0.0001), as well as for the interaction between them (p=0.0001). The results of the Tukey test for the bleaching agent factor regarding the cumulative amount of peroxide were: WHPB-14.04(6.60)a, WHP-19.51(8.61)b, WHPA-23.20(10 ,48)c, POP-26.53(11.13)d, PB 28.29(10.99)de, OPB-31.03(11.81)e, Control-79.12(32.27) )f. For the time factor, in minutes, the results were: 5-9.64(6.70)a, 10-17.42(11.60)b, 15-24.03(16.86)c, 20- 29.50(20.44)d, 25-33.93(23.00)e, 30- 38.41(25.83)f, 35-41.52(27.32)fg, 40-44, 11(28.47)gh, 45-46.50(29.72)h. The results of the repeated measures ANOVA test showed significant differences (p=0.00) in relation to the initial and final peroxide concentration for the factors bleaching agent, reading time and the interaction between them. Bleaching agents with a higher initial concentration of hydrogen peroxide showed a greater cumulative release of the active ingredient; The release of hydrogen peroxide from different whitening gels occurs gradually in relation to the application time, but this release does not occur constantly. (AU)

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A major parameter controlling the extent and rate of oral drug absorption is permeability through the lipid bilayer of intestinal epithelial cells. Here, a biomimetic artificial membrane permeability assay (Franz-PAMPA Pampa) was validated using a Franz cells apparatus. Both high and low permeability drugs (metoprolol and mannitol, respectively) were used as external standards. Biomimetic properties of Franz-PAMPA were also characterized by electron paramagnetic resonance spectroscopy (EPR). Moreover, the permeation profile for eight Biopharmaceutic Classification System (BCS) model drugs cited in the FDA guidance and another six drugs (acyclovir, cimetidine, diclofenac, ibuprofen, piroxicam, and trimethoprim) were measured across Franz-PAMPA. Apparent permeability (Papp) Franz-PAMPA values were correlated with fraction of dose absorbed in humans (Fa%) from the literature. Papp in Caco-2 cells and Corti artificial membrane were likewise compared to Fa% to assess Franz-PAMPA performance. Mannitol and metoprolol Papp values across Franz-PAMPA were lower (3.20 × 10-7 and 1.61 × 10-5 cm/s, respectively) than those obtained across non-impregnated membrane (2.27 × 10-5 and 2.55 × 10-5 cm/s, respectively), confirming lipidic barrier resistivity. Performance of the Franz cell permeation apparatus using an artificial membrane showed acceptable log-linear correlation (R2 = 0.664) with Fa%, as seen for Papp in Caco-2 cells (R2 = 0.805). Data support the validation of the Franz-PAMPA method for use during the drug discovery process.

RESUMEN

The use of sunscreen products is widely promoted by schools, government agencies, and health-related organizations to minimize sunburn and skin damage. In this study, we developed stable solid lipid nanoparticles (SLNs) containing the chemical UV filter octyl methoxycinnamate (OMC). In parallel, we produced similar stable SLNs in which 20% of the OMC content was replaced by the botanical urucum oil. When these SLNs were applied to the skin of human volunteers, no changes in fluorescence lifetimes or redox ratios of the endogenous skin fluorophores were seen, suggesting that the formulations did not induce toxic responses in the skin. Ex vivo (skin diffusion) tests showed no significant penetration. In vitro studies showed that when 20% of the OMC was replaced by urucum oil, there was no reduction in skin protection factor (SPF), suggesting that a decrease in the amount of chemical filter may be a viable alternative for an effective sunscreen, in combination with an antioxidant-rich vegetable oil, such as urucum. There is a strong trend towards increasing safety of sun protection products through reduction in the use of chemical UV filters. This work supports this approach by producing formulations with lower concentrations of OMC, while maintaining the SPF. Further investigations of SPF in vivo are needed to assess the suitability of these formulations for human use.

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ABSTRACT Aiming to alter and/or improve permeation of active compounds in the skin, many strategies have been developed, including biophysical methods. One of the physical absorption techniques, currently known as Cryo Laser Phoresis (CLP), consists of an apparatus that emits radiation on polar or nonpolar molecules of the active substance, resulting in faster penetration when in comparison to the standard topical application. The goal of this work was to evaluate the efficacy of a method that proposes to increase cutaneous permeation of diclofenac sodium by using CLP technique. The influence on permeation was evaluated ex vivo, using Franz cell and human skin obtained from cosmetic surgery. The results were evaluated using statistical methods and data exploratory analysis: clusters, k-means and Principal Component Analysis. The results showed a larger increase in the concentration of diclofenac sodium in the dermis with the use of laser. In all samples (with or without laser application) it was observed that skin surface showed an amount of diclofenac sodium and that there was no active passage to the receptor liquid, suggesting that diclofenac sodium was not absorbed. These results indicate that CLP, when used under the conditions described in this study, is able to increase diclofenac sodium penetration and its retention into deeper layers.

RESUMO No sentido de alterar e/ou melhorar a penetração de substâncias na pele, diversas estratégias têm sido desenvolvidas, variando desde a aplicação de novos veículos e ativos encapsulados, até equipamentos que atuam por métodos biofísicos. Uma das técnicas de absorção física, atualmente conhecida como Crio Laser Forese (CLF), consiste em um aparato que emite radiação sobre moléculas polares ou apolares da substância ativa, tornando sua penetração mais rápida, se comparada à administração tópica comum. O objetivo deste trabalho foi avaliar a eficácia de um método que propõe aumentar a permeação cutânea do diclofenaco de sódio incorporado a um gel, por meio do uso da CLF. A influência sobre a permeação foi avaliada ex vivo, utilizando célula de Franz e pele humana obtida de cirurgia plástica. Os resultados foram balizados mediante aplicação de métodos estatísticos e análise exploratória de dados: clusters, k-means e Análise por Componentes Principais. Os resultados demonstraram aumento na concentração do diclofenaco de sódio na derme com o uso do laser. Em todas as amostras (com ou sem aplicação de laser), observou-se, uma quantidade de diclofenaco de sódio na superfície da pele e que não houve passagem de ativo para o líquido do receptor, sugerindo que o diclofenaco de sódio não foi absorvido. Estes resultados indicam que CLF usada sob as condições descritas neste estudo é capaz de aumentar a penetração do diclofenaco de sódio e sua retenção em camadas mais profundas da pele.

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