*2.2. Preparation of Transdermal Patch*

The solvent evaporation technique was used for the formulation of methotrexateloaded patches, with EC and HPMC as rate-controlling polymers at different concentrations (Table 1). The polymers were weighted accurately using an analytical weighing balance (Shimadzu AX 200, Kyoto, Japan), placed in a solvent system (15 mL) comprising ethanol and dichloromethane (1:1) and allowed to swell for 6 h. The plasticizer used was PEG-400. A 100 μL volume of ethanolic hydrochloric acid was taken in a beaker, and a proper amount of methotrexate was added. Dichloromethane and ethanol (1:1) were taken in a separate beaker and placed in a sonicator (Elma D-78224, Germany) for 2 min. The drug and polymers were mixed homogeneously by slow stirring. A uniform dispersion was poured in Petri dishes with an area of 19.5 cm2. The Petri dishes were placed in an oven (Memmert, Germany) at 40 ◦C for 12 h.


