3±4.6%, however the difference was found to be insignificant (f2>50; Fig. 6). The observed increase of drug release

with higher amount of alcohol could be due to increased fluidity of the bilayer membrane with increasing concentration of alcohol. To assess BMN 673 supplier the release rate kinetic value, values of diffusional release exponent was calculated by plotting log cumulative amount of drug release versus log time (graph not shown). Formulations exhibited diffusional release exponent in the range of 0.7093–0.7414 indicating non-Fickian release of drug from the vesicular system. Overall with in vitro release through cellophane membrane it can be summed up that all the formulations showed sustained behavior compared to hydroalcoholic drug solution. The permeation profile of various formulations through the skin was compared with that obtained from hydroalcoholic drug solution. The cumulative

amount of drug permeated from various ethosomal formulations was found to be significantly higher (p<0.05) in comparison to permeation from hydroalcoholic drug solution. The value of f2 for all the formulations was found to be less than 50 in comparison to hydroalcoholic drug solution indicating significant difference. Values of steady state transdermal flux were calculated from the graph of cumulative drug permeated versus time CB-839 solubility dmso and are shown in Table 1. Enhancement ratio was calculated by dividing transdermal flux of ethosomal formulations to that of control. Transdermal flux from various ethosomal formulations across skin was ranged between 165.7±19 to 207.1±23.3 μg/cm2/h whereas lower transdermal flux 94.6±10.3 μg/cm2/h was observed with hydroalcoholic Dimethyl sulfoxide drug solution ( Table 1). Three dimensional surface plot was prepared to check the influence of composition of ingredients of formulation i.e. SPC and alcohol on transdermal flux ( Fig. 7). It is clear from the surface plot and Fig. 8 that the highest transdermal flux is observed with a ethosomal

formulation having 1% SPC and 40% ethanol (E3). The concentration of alcohol has more influence on transdermal flux compared to the amount of SPC. Two zones of higher transdermal flux (198.8–240.4 and 204.4–210 μg/cm2/h) are seen with formulations having 1–1.75% of SPC and 35–40% of alcohol. However when the concentration of alcohol is decreased to 20–25% with around the same amount of SPC (1.25–2.25%), the zone with lowest transdermal flux is reached. Formulation E1, which is composed of 1% SPC and 20% alcohol showed permeation of 3211.8±36.6 μg drug after 24 h, this was significantly increased to 3529.5±59.1 and 3840±25.2 μg when the concentration of alcohol was increased to 30% and 40% respectively (f2<50) ( Fig. 8). Formulation E3, which was composed of the lowest vesicle size, outperformed all other formulations and showed the highest transdermal flux.