A revolutionary drug delivery method called transdermal delivery eliminates a number of obstacles in drug therapy, including the requirement for assistance, intermediate dosage, and painful administration. In comparison to traditional drug delivery methods, transdermal distribution has various benefits, including the avoidance of hepatic first pass metabolism, a potential reduction in side effects, and an increase in patient compliance. In the present study, the focus was on the development of Macitentan nanoparticle loaded transdermal patch by using solvent displacement technique or nano precipitation method. Particle size and distribution were two important factors influencing the drug's penetration. The drug content, entrapment efficiency, zeta potential, particle size, and in vitro diffusion experiments were used to characterize the produced nanoparticles. The mean size of all six formulations was modest, which is appropriate for a transdermal administration technique. Transdermal patches loaded with macitentan nanoparticles were made using Eudragit RS 100, and varying percentages of ethyl cellulose. The results indicated that the strategy adopted, viz, preparation of Macitentan polymeric nanoparticles and incorporation of these prepared nanoparticles into a transdermal patch, will successful in enhancing the permeation of drug nanoparticles. As the concentration of the polymer increased, there was an increase in the thickness of the patch.