Prediction of steady state in vivo drug plasma concentration was based on assumption that drug were in a patch of 50 cm2. To check the kinetics of in vitro permeation, the diffusional release exponent was calculated. Diffusional release exponent was estimated as slope of the graph plotted between log cumulative amounts of drug release versus log time (graph not shown). The diffusional release exponent is a parameter that is indicative of drug release mechanism. A diffusional release exponent of 0.5 indicates normal concentration-controlled Fickian diffusion (case I). Exponent of 1 indicates CX-5461 mouse zero order release (case II) while its value more than

1 indicates super case II type release. The value of diffusional release exponent for all the formulations was found to be around one which indicates that absorption of drugs through the skin follows zero order release. Systems that obey Entinostat zero order release are ideal for transdermal drug delivery as they provide constant release of drug over an extended period of time and reflect improved therapeutic index. The kinetics of ketoprofen across skin (zero order) is different from that across cellophane membrane (non-Fickian). This may be due to the fact

that skin has complex structure and release profile of drugs from delivery system through skin cannot be exactly matched with cellophane membrane. It may suggest that other than the ethosome itself, skin also modified the diffusion properties of ketoprofen. This can be explained in a way that some component of the skin might be interacting with the ethosomes and altering its diffusional properties. The increased drug skin permeability with ethosomal formulations is concordant with the reports published in literature showing enhanced drug permeation with lipid vesicles having ethanol as one of components [4], [8], [27] and [37]. Alcohol is a natural enhancer, which has the property to alter the skin permeability. However transdermal permeability of ethosomal formulations was found to be higher compared to hydroalcoholic

drug solution which indicates that it is not alcohol alone which is contributing for higher skin permeability. Several studies have investigated the possible mechanism for improved skin permeability with lipid vesicular system. Vesicles can act as a carrier of drug and intact vesicles penetrate the stratum Thymidine kinase corneum along with the encapsulated drug. Secondly vesicles can act as penetration enhancer and interacts with the stratum corneum lipids and alter the permeability, which facilitates penetration of drug molecule across stratum corneum. Enhanced permeation of drug with ethosomal formulations could be due to combined effect of alcohol and lipid vesicular system. Skin is a densely packed organ and lipids are arranged in a symmetric conformation. Alcohol being a penetration enhancer might interact with the skin lipid and disturbs its conformation with consequent increase in fluidity.