Designing of carrier system for model drugs and evaluation their transdermal flux via concentration-current gradient

The aim of the study is to design carrier system for transdermal delivery of model drugs Donepezil and Memantin and to investigate the effect of concentration and current intensity on the amounts of drug passing through this system to the systemic circulation. Polymer matrix including EPO, HPMC and EC were used to obtain monolayer films. PEG was used as plasticizer at 30% w/w and glycerol was used to maintain the moisture content of the formulation at 30% w/w, relative to the polymer matrix. The drugs were loaded at two concentrations (2 mg & 10 mg) to monolayer films which has a 2.55 cm2 constant surface area. Anodal iontophoresis was applied for 1 hour with a current intensity of 0.1 mA/cm2 or 0.5 mA/cm2 on loaded monolayer films which were placed on shaved dorsal skins of rats. The results obtained by iontophoresis were compared with the results of passive diffusion and IV administration. In order to evaluate the relationship between in vitro and in vivo conditions correlation curves were generated. The used model drugs have similar physicochemical properties but, Memantin has more hydrophobic and lower molecular weight compared to Donepezil. The passive diffusion blood samples concentration of Memantin was 166.13 ng/mL/24 h and increased to 10.59 µg/mL/24 h after 1 hour 0.5 mA/cm2 anodal iontophoresis of Memantin loaded monolayer films. The passive diffusion blood samples concentration of Donepezil was 73.56 ng/mL/24 h and increased to 636.81 ng/mL/24 h after 1 hour 0.5 mA/cm2 anodal iontophoresis of Donepezil loaded monolayer films. The results showed that increase in concentration and current intensity were effective in increasing the transport of model drugs through the skin, it was observed that the increase in transport quantity was depended on physicochemical properties of the model drugs. Key Words: Donepezil, Memantin, Flux, Transdermal, Iontophoresis, Current intensity, Concentration