Development and Characterization of a Leflunomide-Loaded Liposomal Gel as a Novel Topical Drug Delivery System

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder characterized by persistent joint inflammation and progressive tissue damage. Leflunomide (LEF) is a disease-modifying antirheumatic drug (DMARD) used in the management of RA. Its active metabolite, teriflunomide, inhibits dihydroorotate dehydrogenase (DHODH), thereby interfering with pyrimidine synthesis and reducing lymphocyte proliferation. However, conventional systemic administration of LEF is associated with limitations such as prolonged half-life, slow elimination, and hepatotoxicity. Therefore, the present study aimed to develop a liposomal gel of leflunomide as a novel topical drug delivery system. Preformulation studies were performed to evaluate the physical characteristics, melting point, and solubility of leflunomide. The drug was found to be a white to off-white crystalline powder with a melting point of 150–153°C and showed poor aqueous solubility. The maximum absorption wavelength of leflunomide in ethanol was determined to be 260 nm using UV-visible spectroscopy. Leflunomide-loaded liposomes were prepared using the ethanol injection method with soy lecithin and cholesterol as lipid components. The prepared liposomes weresubsequently incorporated into a Carbopol-based gel. The developed liposomal gel was evaluated for viscosity, spreadability, pH, particle size, zeta potential, entrapment efficiency, and in-vitro drug release. The formulation exhibited a skin-compatible pH of 6.1 and demonstrated sustained drug release over 24 h, with approximately 85% drug release. The findings indicate that leflunomide-loaded liposomal gel may serve as a promising approach for topical drug delivery and sustained release of leflunomide.