Trandolapril is an Angiotensin Converting Enzyme (ACE) inhibitor, it belongs to the BCS class II. The current study encompasses the formulation of novel nanoparticles loaded transdermal patches of Trandolapril with the aid of Box Behnken Design. Pre-formulation studies such as identification of the drug by FT-IR, the estimation of the drug by UV spectroscopy and the melting point determination were performed. The nanoparticles were formulated by solvent emulsification evaporation method using Compritol 888 ATO as lipid, Span 60 and Tween 80 as surfactants to improve the physicochemical properties of Trandolapril . The prepared nanoparticles were evaluated for particle size, polydispersity index, zeta potential, entrapment efficiency, drug content and in-vitro drug release studies and the evaluated data was used to carry out numerical optimization to obtain the best formulation with the optimum concentration of excipients. The optimized concentration for independent variables Trandolapril (X1), Compritol 888 ATO (X2), and Span 60 (X3) were found to be 75mg, 2000mg, and 60mg respectively, with the desirability of 0.916.The optimized formulation of Nanoparticles were then loaded into a HPMC-E50-based transdermal patch by solvent casting method to overcome the restricted bioavailability of Trandolapril . The thickness, folding endurance, weight uniformity, drug content and in-vitro drug release of the patch were evaluated. The drug release from the patch was found to be greater than the release from the solid lipid nanoparticles. The reason could be due to the intimate contact of the patch to the skin and the use of a penetration enhancer in the patch formulation. In conclusion, the results obtained suggest that a patch formulation containing nanoparticulate system is a potentially promising formulation for the efficient delivery of Trandolapril through skin