RESUMO
An optimization technique (response surface method) was used in order to investigate the effect of the combination of two enhancers, namely caprylic acid and cineol on nimodipine's permeation through human cadaver epidermis. Using this quadratic model it was found that at 24 h the increase of the permeation of nimodipine it was mainly due to the effect of caprylic acid. On the contrary, it was shown that at 48 and 72 h the combination of the two enhancers contributed to the increase of the permeation. The greater Q(gel)/Q(control) values, at all time intervals (24, 48 and 72 h), were obtained when the concentration of cineol and caprylic acid range from 3.0 to 5.0% (v/v) and 8.0 to 9.5% (v/v), respectively.
Assuntos
Bloqueadores dos Canais de Cálcio/química , Bloqueadores dos Canais de Cálcio/farmacocinética , Monoterpenos , Nimodipina/química , Nimodipina/farmacologia , Algoritmos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Caprilatos/farmacologia , Cromatografia Líquida de Alta Pressão , Cicloexanóis/farmacologia , Eucaliptol , Excipientes , Géis , Humanos , Técnicas In Vitro , Modelos Estatísticos , Nimodipina/administração & dosagem , Absorção Cutânea/efeitos dos fármacos , Terpenos/farmacologiaRESUMO
The in vitro permeation of nimodipine through human cadaver skin, as a preliminary step toward the development of a transdermal therapeutic system, was investigated. In vitro release studies were carried out using modified Franz diffusion cells and human epidermal membrane, taken from full-thickness cadaver skin by heat separation technique. To estimate the effect of the type of enhancer, the concentration of enhancer and the concentration of the gelling agent on the permeation of nimodipine, a 2(3) factorial design was involved. The type of enhancer was further evaluated, because it was found to be important for the permeation of nimodipine; the concentration of enhancer and the concentration of the gelling agent were kept at their optimum levels in all experiments. Six groups of enhancers (alkanols, alkanoic acids, alkanoic acids ethyl esters, caprylic acid alkyl esters, essential oils and some other enhancers) were examined for their ability to increase the permeation of nimodipine. It was found that myristyl alcohol, caprylic acid, L-menthol, and oleic acid gave better permeation rates at 24 hr, with oleic acid being the better enhancer, and higher permeation rates at 48 and 72 hr were achieved only when cineol was used.
