Combination of excimer laser and topical treatment for psoriasis: A systematic review and meta-analysis

@#<p style="text-align: justify;"><strong>OBJECTIVES: </strong>To assess the efficacy and safety of excimer laser in combination with topical standard therapies for treatment of plaque-type psoriasis in comparison to excimer laser alone, standard topical treatment alone, or placebo.</p><p style="text-align: justify;"><strong>METHODS: </strong>A literature search using Medline, Cochrane and HERDIN was conducted. Data were analyzed using mean difference at 95% confidence interval, with heterogeneity determined by I2 test.</p><p style="text-align: justify;"><strong>RESULTS:</strong> Three articles with total of 130 patients fulfilled the inclusion criteria. Topical treatments studied were vitamin analog (calcipotriol), anthralin (dithranol), and steroid (flumethasone pivalate). A subgroup analysis comparing combination therapy and excimer laser alone showed a greater reduction in pooled PASI score reduction (-2.52; 95% CI: -4.28, -0.77) in the combination group after five to six weeks. There was also a significantly greater reduction in cumulative UVB dose (-3.29; 95% CI: -4.29, -2.30) needed for clearing in the combination group. Pigmentation was the commonly observed adverse event in both groups.</p><p style="text-align: justify;"><strong>CONCLUSIONS:</strong> Excimer laser, in combination with topical treatment, is more effective than excimer laser alone, with significantly lower cumulative UVB dose, but the quality of current evidence is low. Long-term controlled trials are warranted to increase our confidence in the estimates of these outcomes.</p>

Synthesis and antibacterial activity of some 3-(5-aryl-4H-pyrazol-3-yl).

A series of 3-(5-aryl-4H-pyrazol-3-yl)anthracen-10(9H)-ones were synthesized from anthracen-10(9H)-one (1) and studied for their in vitro antibacterial activity. Anthracen- 10(9H)-one after Friedel crafts acetylation with acetyl chloride yielded 3-acetylanthracen- 10(9H)-one (2) which on further reaction with substituted aromatic aldehydes in the presence of catalytic amount of sodium hydroxide in water and ethanol furnished the corresponding 3-(3-arylacryloyl)anthracen-10(9H)-ones (3a-g) as intermediate compounds, which on further reaction with hydrazine hydrate in absolute ethanol formed the title compounds 3-(5-aryl-4H-pyrazol-3-yl)anthracen-10(9H)-ones (4a-g). These compounds were characterized by elemental analysis, IR, Mass and 1H-NMR spectral data. All the compounds were evaluated for their in vitro antibacterial activity against two gram positive strains (Bacillus subtilis and Staphylococcus aureus) and two gram negative strains (Escherichia coli and Pseudomonas aeruginosa) taking ciprofloxacin as a standard drug. Some of the compounds showed significant antibacterial activity.

Use of solid dispersions to increase stability of dithranol in topical formulations

The present study was planned to improve the stability of dithranol using solid dispersions (SD). Two different SD at a 1:9 ratio of dithranol/excipient were prepared: one of them using glyceryl behenate as excipient and the other using a mixture of argan oil with stearic acid (1:8 ratio) as excipient. Pure dithranol and SD of dithranol were incorporated in an oil-in-water cream and in a hydrophobic ointment in a drug/dermatological base ratio of 1:10. The physical and mechanical properties of semisolid formulations incorporating the pure drug and the developed SD were evaluated through rheological and textural analysis. To evaluate the stability, L*a*b* color space parameters of SD and semisolid formulations, and pH of hydrophilic formulations were determined at defined times, during one month. Each sample was stored at different conditions namely, light exposure (room temperature), high temperature exposition (37 °C) (protected from light) and protected from light (room temperature). Despite higher values of firmness and adhesiveness, hydrophobic ointment exhibited the best rheological features compared to the oil-in-water cream, namely a shear-thinning behavior and high thixotropy. These formulations have also presented more stability, with minor changes in L*a*b* color space parameters. The results of this study indicate that is possible to conclude that the developed SD contributed to the increased stability of dithranol.

Este trabalho teve como objetivo aumentar a estabalidade do ditranol através da preparação de dispersões sólidas (DS). Prepararam-se duas DS diferentes em proporção de 1:9 de ditranol/excipiente: em uma das DS utilizou-se beenato de glicerila como excipiente e na outra se utilizou mistura de óleo de argan com ácido esteárico (razão 1:8). Posteriormente, efetuou-se a incorporação de ditranol puro e das DS contendo este fármaco num creme hidrófilo ou óleo-água (O/A) e em pomada hidrófoba, na proporção 1:10 (fármaco ou respetivas DS/base dermatológica). As propriedades físicas e mecânicas das formulações semissólidas incorporando fármaco ou as respetivas DS previamente desenvolvidas, foram avaliadas através da análise do comportamento reológico e das propriedades de textura. Para avaliar a estabilidade, os parâmetros do espaço de cor L*a*b* das DS e das formulações semissólidas e o pH das preparações hidrófilas foram determinados em períodos de tempo definidos, durante um mês para cada amostra armazenada sob diferentes condições, especificamente, exposição à luz (à temperatura ambiente), protegidas da luz à temperatura elevada (37 °C) e protegidas da luz (temperatura ambiente). Embora tenham apresentado valores de firmeza e de adesividade mais elevados, as pomadas hidrófobas apresentaram melhores características reológicas do que os cremes óleo-água. Além disso, as pomadas hidrófobas também apresentaram melhor estabilidade, com pequenas alterações nos parâmetros do espaço de cor L*a*b*. Os resultados deste trabalho permitiram concluir que as DS desenvolvidas contribuíram para o aumento da estabilidade do ditranol.

Preformulations studies and preperation of dithranol loaded solid lipid nanoparticles.

Dithranol belongs to the keratolytic category, which is widely used drug in the treatment of psoriasis. The drug is practically insoluble in water. Many conventional dosage forms for psoriasis treatment have been have been formulated earlier, but they did not show good results. Hence in the present study, it was attempted to formulate dithranol in the form of solid lipid nanoparticle. Solid lipid nanoparticles of dithranol were obtained by adaption of lipid dispersion method. Preformulation studies were performed to check the compatibility of drug and excepient for the preparation of formulation by DSC and no interaction was found. Solubility study, partition coefficient determination, UV analysis, HPLC study, FTIR study were also performed. After the preformulation studies Dithranol loaded solid lipid nanoparticles was also prepared. Hence it was concluded that solid lipid nanoparticle of dithranol could be formulated.

Statistical optimization of dithranol-loaded solid lipid nanoparticles using factorial design / Otimização estatística de nanopartículas lipídicas sólidas carregadas com ditranol utilizando planejamento fatorial

This study describes a 3² full factorial experimental design to optimize the formulation of dithranol (DTH) loaded solid lipid nanoparticles (SLN) by the pre-emulsion ultrasonication method. The variables drug: lipid ratio and sonication time were studied at three levels and arranged in a 3² factorial design to study the influence on the response variables particle size and percent entrapment efficiency ( percentEE). From the statistical analysis of data polynomial equations were generated. The particle size and percentEE for the 9 batches (R1 to R9) showed a wide variation of 219-348 nm and 51.33- 71.80 percent, respectively. The physical characteristics of DTH-loaded SLN were evaluated using a particle size analyzer, differential scanning calorimetry and X-ray diffraction. The results of the optimized formulation showed an average particle size of 219 nm and entrapment efficiency of 69.88 percent. Ex-vivo drug penetration using rat skin showed about a 2-fold increase in localization of DTH in skin as compared to the marketed preparation of DTH.

Este estudo descreve o planejamento factorial 3² para otimizar a formulação de nanopartículas lipídicas sólidas (SLN) carregadas com ditranol (DTH) pelo método da ultrassonificação pré-emulsão. As variáveis como proporção de fármaco:lipídio e o tempo de sonicação foram estudados em três níveis e arranjados em planejamento fatorial 3² para estudar a influência nas variáveis de resposta tamanho de partícula e eficiência percentual de retenção do fármaco ( por centoEE). Pela análise estatística, geraram-se equações polinomiais. O tamanho da partícula e a por centoEE para os 9 lotes (R1 a R9) mostraram ampla variação, respectivamente, 219-348 nm e 51,33-71,80 por cento. As características físicas das SLN carregadas com DTN foram avaliadas utilizando-se analisador de tamanho de partícula, calorimetria de varredura diferencial e difração de raios X. Os resultados da formulação otimizada mostraram tamanho médio de partícula de 219 nm e eficiência de retenção do fármaco de 69,88 por cento. A penetração ex vivo do fármaco utilizando pele de rato mostrou aumento de, aproximadamente, duas vezes na localização de DTH na pele, comparativamente à preparação de DTH comercializada.