Rheumatoid arthritis is a chronic inflammatory illness that affects many elderly people's quality of life. Combinational DMARDs are a new therapeutic approach in managing disease conditions, based on the concept that the two medications work in two distinct routes to diminish (or) delay disease development.This study aimed to develop and improve the pharmacokinetic and safety margin of SLN as an MTX carrier in vitro. As a result, an attempt was made to construct SLN for the delivery of MTX and DOX and to evaluate size, stability, and drug release characteristics.Methods: supplied the methotrexate (Chennai, India). Micro Labs Pvt. Ltd provided the Doxycycline (Hosur, India). Tokyo Chemicals Industries provided the tristearin. Himedia Laboratories Pvt. Ltd provided stearic acid, Pluronic F68, Dialysis Membrane, and Membrane Filter (Mumbai, India).