**2. Materials and Methods**

### *2.1. Materials*

Methotrexate was kindly gifted by Wilsons Pharmaceutical (Pvt.) Ltd., Pakistan. Ethyl cellulose (EC) and hydroxypropyl methyl cellulose (HPMC) (Dow Chemical Company, 693 Washington St, #627, Midland, MI, 48640, USA, +1-989-636-1000) were used as ratecontrolling polymers. Ethanol (Sigma-Aldrich Inc., P.O. Box 14508, St. Louis, MO, 63178, USA, +1-314-771-5750), PEG-400 (Sigma-Aldrich Co., 3050 Spruce Street, St. Louis, MO, 63103, USA, +1-314-771-5765), sodium hydroxide (NaOH) (Sigma-Aldrich Chemie GmbH, Riedstrasse 2, 89555 Steinheim, Germany, +49-7329-970), dichloromethane and calcium chloride (Dow Chemical Co., 2030 Dow Ctr, Midland, MI, 48674, USA, +1-989-638-8173) were used in the preparation of patches and buffers. Analytical-grade chemicals were used in this study.
