Enhanced Controlled Transdermal Delivery of Torasemide Using Ethylene-vinyl Acetate

Purpose: To develop an ethylene-vinyl acetate (EVA) matrix system containing a permeation enhancer for enhanced transdermal delivery of torasemide. Methods: The solubility of torasemide was studied at various volume fraction of polyethylene glycol (PEG) 400. The effect of drug concentration was tested at 1.0, 2.0 and 3.0 %, respectively while the effect of temperature on drug release from drug-EVA matrix was evaluated at 27, 32, 37 and 42 degrees C. To increase pore size and flexibility of the EVA matrix, plasticizers with citrate and phthalate groups were added to the matrix containing torasemide. To improve the penetration of torasemide from the EVA matrix across the skin, enhancers (propylene glycol derivatives, fatty acids, glycerides, pyrrolidones and non-ionic surfactants) were incorporated into the torasemide-EVA matrix. The effects of the enhancers on the skin penetration were evaluated using Franz diffusion cell fitted with the intact excised rat skin. Results: Solubility and permeation of torasemide was highest at 40 %v/v PEG 400. The release rate of drug from drug-EVA matrix increased with increased loading dose and temperature. Release rate was proportional to the square root of loading dose. The activation energy (E-a), which was derived from the slope of log P versus 1000/T, was 14.95 kcal/mol for 2.0% loading dose. Among the plasticizers used, diethyl phthalate showed the highest release rate of torasemide. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the greatest enhancing effect. Conclusion: For the enhanced controlled transdermal delivery of torasemide, the application of the EVA matrix containing plasticizer and penetration enhancer could be useful in the development of a transdermal drug delivery system.