Thisworkdescribetheformulation and characterization of Ondansetron HCL transdermal patchestomanage and deliverdrugcontentinappropriatemanner. The purpose of this research study focused on the development of polymer base transdermal films containing Ondansetron HCL by solvent evaporation technique and analysis of dissolution kinetics. Auxiliary substances represented an important role in pharmaceutical forms, in first stage, drug content and excipients compatibility were performed and verifiedbetween TDS1 9.80 ± 0.125 μg·cm−2·h−1TDS3 20.12 ± 0.125 μg·cm−2·h−1 and TDS8 22.11 ± 0.125 μg·cm−2·h−1. Release studies were done at36°C transdermal drug delivery system ex-vivo drug permeation study was found optimized results. In-vitro drug release kinetics were done at 32 °C ± 1 °C with a Franz diffusion cell. The results obtained were analysed and confirms the active substances with two matrix-forming polymers of FT-IR. At pH 5.5 to 7.4, flux values were between 15.22 ± 0.125 μg·cm−2·h−1, 20.12 ± 0.380 μg·cm−2·h−1; 30.12 ± 0.380 μg·cm−2·h−1; 40.2 ± 0.380 μg·cm−2·h−1; 22.11 ± 0.380 μg·cm−2·h−1; 30.14 ± 0.380 μg·cm−2·h−1; 50.11 ± 0.380 μg·cm−2·h−1. Thisstudyconfirmed therate of penetration and creatingnovelapproaches of Ondansetron HCL deliverywithpolymersolution. Thisnovelapproachesof Ondansetron HCL loaded transdermal patcheshasincreasedtheapplication of antiemeticdrug of theirconventionalroutes of drugadministrationviaskindelivery.