​Matrix transdermal drug delivery systems were successfully prepared, using EVA as a backing layer and ERL and ERS as rate controlling polymers, for controlled release of TMS by solution casting. TEC and DBP were used as plasticizers and CAPM and CAPX were used as penetration enhancers. All patches were transparent, clear, flexible and uniform in thickness, weight and drug content. The HPLC method was found suitable for TMS analysis under experimental conditions of this work, which included drug storage and analysis over a period of 7 days. TMS was stable in the mobile phase, in phosphate buffer and in presence of human skin for 7 days. Moreover, TMS was stable under exposure to light or heat. The type of polymer and additive used affected the properties of the resultant patches. ERL patches had higher moisture uptake values than ERS patches and patches plasticized with TEC had higher moisture uptake values than those plasticized with DBP. In vitro release of TMS from transdermal patches was significantly higher for patches containing TEC as plasticizers compared with those plasticized with DBP. TMS release from patches composed of ERL polymer was significantly higher than that from transdermal patches composed of ERS polymer. In vitro permeation studies showed higher drug permeation from suspension than from solution, due to the higher drug content in suspension which resulted in saturation of the drug in the donor compartment. Addition of penetration enhancers resulted in improved drug permeation. CAPM showed higher TMS permeation and lower lag time than CAPX. Moreover, higher enhancer content resulted in better drug permeation. Combination of enhancers resulted in even further improvement of drug permeation, at a lower concentration of each enhancer. The adhesion force between the transdermal patch and human skin was affected by the type and concentration of additives used. TMS is a charged molecule and cannot easily permeate the stratum corneum. The study, therefore, attempted to establish the TDDS of TMS using simple formulation consisting of two layers; the backing layer and the drug-loaded adhesive layer. The required permeated amount of TMS per day was achieved which might be considered a successful achievement. The study for the first time has shown a relatively high correlation between Strat-M® synthetic membrane and stratum corneum of human skin for 168 h, while other studies did not exceed 24 h​.