Development and in vitro evaluation of nimodipine transdermal formulations using factorial design

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.