eng Oriental Scientific Publishing Company Biosciences Biotechnology Research Asia 0973-1245 2025-12-30 22 4 1529 1540 10.13005/bbra/3458 57286 article Mellacheruvu Punyavathi Kusuma 1 Vedhasree 1 Sumakanth 1 Aparna Peri 1 Department of Pharmaceutical Sciences, RBVRR Women’s college of Pharmacy, Hyderabad, India This study deals with the formulation of transdermal patches containing Papain using the solvent evaporation method employing  central composite design of experiments. 27 formulations were done using different combinations using hydrophilic polymers (HPMCK15, PVP, Eudragit) and hydrophobic polymers (ethyl cellulose), along with solvents (methanol, distilled water, dichloromethane), plasticizer (PEG), and backing membrane (glycerine). The formulations were evaluated based on thickness, folding endurance, transparency, in vitro drug release, and physicochemical properties. Through comprehensive  analysis, formulations F10 to F27 were eliminated, and the remaining formulations (F1-F10) were compared. F1 exhibited the highest folding endurance and  invitro drug release at 7h were in the order F1>F6>F3>F4>F2>F5>F7>F9>F8. The above results are in good agreement with DOE.Thus developing a transdermal system of papain is more selective for site-specific analgesic avoiding gastrointestinal incompatibility. These findings were in agreement with the predicted model, demonstrating the optimised nature of the F1 formulation. Ex vivo studies validated the in vitro results, indicating stability for up to 3 months and maximum antioxidant activity. https://www.biotech-asia.org/vol22no4/formulation-and-evaluation-of-papain-transdermal-patches-using-central-composite-design/ Antioxidant; Central composite design; Eudragit; Papain; Polymers; Transdermal patch