Liquid crystalline systems containing Vitamin E TPGS for the controlled transdermal nicotine delivery

ABSTRACT Transdermal nicotine patches have been used in smoking cessation therapy, suggested for the treatment of skin disorders with eosinophilic infiltration and have been found to improve attention performance in patients with Alzheimer's disease and age-associated memory impairment. However, skin irritation with extended patch use is still a problem. The aim of this work was to develop a simple to prepare liquid crystalline system containing vitamin E TPGS that would be able to control nicotine delivery and reduce irritation and sensitization problems. The liquid crystalline phases were macroscopically characterized by visual analysis and examined microscopically under a polarized light microscope. Topical and transdermal delivery of nicotine were investigated in vitro using porcine ear skin mounted on a Franz diffusion cell. Nicotine skin permeation from the developed cubic phase followed zero-order kinetics (r = 0.993) and was significantly enhanced after 12 h when compared to the control formulation (nicotine solution) (p < 0.05) (138.86 ± 20.44 and 64.91 ± 4.06 μg/cm2, respectively). Cubic phase was also able to target viable skin layers in comparison to control solution (8.18 ± 1.89 and 2.63 ± 2.51 μg/cm2, respectively). Further studies to evaluate skin sensitization and irritation are now necessary.

RESUMO Adesivos transdérmicos de nicotina são utilizados para cessação de fumar, tratamento de problemas de pele com infiltração de eosinófilos e para melhorar a atenção em pacientes com doença de Alzheimer e enfraquecimento da memória associada à idade. No entanto, a irritação da pele com o uso prolongado dos adesivos ainda é um problema. O objetivo deste trabalho foi desenvolver sistema líquido cristalino (SLC) de preparo simples contendo vitamina E TPGS capaz de controlar a liberação de nicotina e reduzir os problemas de irritação cutânea. Os SLCs foram caracterizados por análise visual e microscopia de luz polarizada. As administrações tópica e transdérmica de nicotina foram investigadas in vitro utilizando pele de orelha de porco em célula de difusão de Franz. A permeação da nicotina veiculada pela fase cúbica desenvolvida seguiu cinética de ordem zero (r = 0,993) e foi significativamente maior do que o controle (solução de nicotina) após 12 h (p < 0,05) (138,86 ± 20,44 e 64,91 ± 4,06 µg/cm2, respectivamente). A fase cúbica também promoveu aumento da penetração de nicotina nas camadas viáveis da pele quando comparado ao controle (8,18 ± 1,89 e 2,63 ± 2,51 µg/cm2, respectivamente). Estudos futuros para avaliar a sensibilização e irritação da pele são necessários.

in-vitro iontophoretic permeation study of nicotine through rat skin

Nicotine transdermal systems are being used as an aid to smoking cessation programs. As the kinetics of nicotine delivery is important in success of a smoking cessation program, rapid and high input of nicotine is required, which is not possible by passive methods and requires enhancement strategies such as iontophoresis. Iontophoretic permeation, of nicotine looks promising, based on published data on human skin. However, to optimize this method, permeation pathways should be known and further parameters have to studied, which are the subject of the present investigation. In this study iontophoretic permeation of nicotine through rat skin was performed and the effects of different variables on this phenomenon were studied. Anodic iontophoresis of nicotine from a solution at pH 2.8, using a 0.5 mA/cm[2] current density resulted in a considerable enhancement [about 3-fold] of nicotine absorption through rat skin. Nicotine concentration and current density showed a directly increasing effect on permeation of the drug, but the effect of concentration was not linear. Pulsatile current delivery was more effective in permeation of nicotine than the continuous method. Anodic iontophoresis was around 2-fold more effective than the cathodic method in increasing the flux. Post iontophoretic permeation studies showed good reversibility of the membrane barrier properties. Results were in good agreement with the reported human data and might be considered as an evidence of the ability of rat skin to model human skin and also the importance of intercellular pathway of the stratum corneum in iontophoretic delivery of nicotine and possibly other drugs. Donor's pH showed no effect on permeation of nicotine under the studied conditions, pH values of <3. Results also showed that the electr-osmotic flow could occur at pH values lower than 4. Finally, this study show that by controlling the effective parameters of iontophoretic delivery, a more effective nicotine transdermal delivery method would achievable

Nistagmo espontáneo y posicional por efecto de la intoxicación aguda por drogas y sustancias químicas en humanos / Spontaneous and positional nystagmus due to acute intoxication by drugs and chemical substances in human

Se realizó una intoxicación experimental en 70 personas jóvenes normales que produjo vértigo o desequilibrio. Se estudiaron dos parámetros: el nistagmo espontáneo y el posicional. Las drogas que se experimentaron fueron de uso común mientras que otras se usan por prescripción terapéutica. Estas drogas actúan sobre la homeostasis del sentido del equilibrio sea por efecto inhibitorio o exitatorio en diferentes niveles del sistema nervioso central. Las sustancias estudiadas fueron: alcohol, ketamina, pentobarbital, nicotina, xileno, etambutol, tricloroetileno, fentanil y droperidol. Todas las drogas, con excepción de la ketamina, produjeron nistagmo espontáneo y porsicional, en algunas personas contra la gravedad y en las otras a favor de ella. La información obtenida lo conduce a uno a predecir cuán mal se sentirá una persona después del uso de drogas como las fenotiazinas, dependiendo del nivel del sistema nervioso que es afectado o cuán bien se sentirá usando un agonista del GABA o un antagonista de acetilcolina, dependiendo del tipo del nistagmo espontáneo o posicional que afecte al paciente en el momento de usar alguna de estas drogas

Substrato neuroquímico de la farmacología conductual del etanol / Neurochemical substrate of the behavioral pharmacology of ethanol

Este artículo constituye una revisión del substrato neuroquímico de los efectos conductuales del etanol (ETOH), en especial sus propiedades gratificantes positivas y la tolerancia y dependencia física que su consumo produce, a partir de estudios en animales, haciendo referencia también a resultados obtenidos en humanos. La mayoría de los sistemas de neurotransmisión están involucrados en las acciones conductuales del ETOH, principalmente las monoaminas y los opioides. Sus efectos depresores a altas dosis, estimulantes a bajas dosis e hipotérmicos parecen tener bases distintas. Mientras que la activación catecolaminérgica está relacionada con los efectos estimulantes, los mecanismos gabérgicos están más involucrados con los depresores