Formulation and Evaluation ofTransdermal Patch of Leflunomide,Piroxicam, and Methotrexate for theTreatment of Rheumatoid Arthritis

Abstract

Background: Rheumatoid Arthritis is a chronic autoimmune disease that requires prolonged therapeutic
management. Conventional oral administration of anti-rheumatic drugs is often associated with gastrointestinal
side effects, poor patient compliance, and fluctuating plasma drug concentrations. The present study was aimed at
formulating and evaluating a combination transdermal patch containing Leflunomide, Piroxicam, and Methotrexate
for controlled and effective treatment of rheumatoid arthritis. Materials and Methods: Transdermal patches were
prepared using the solvent casting method with different ratios of hydrophilic polymer HPMC and hydrophobic
polymer Ethyl Cellulose. Analytical methods including UV spectrophotometry and RP-HPLC were developed
and validated for simultaneous estimation of the drugs. Preformulation studies such as organoleptic evaluation,
solubility analysis, melting point determination, and compatibility studies were performed to assess drug purity
and drug–excipient interactions. The formulated patches were evaluated for physicochemical parameters,
mechanical properties, drug content uniformity, in-vitro drug diffusion, in-vivo pharmacokinetic performance, and
stability under accelerated conditions. Results and Discussion: Compatibility studies confirmed the absence of
significant drug–excipient interactions, indicating formulation stability. The prepared patches showed satisfactory
thickness, folding endurance, moisture content, tensile strength, and uniform drug distribution. In-vitro diffusion
studies demonstrated sustained and controlled drug release for up to 24 hours. Pharmacokinetic studies revealed
enhanced bioavailability, prolonged therapeutic action, and reduced plasma concentration fluctuations compared
to conventional oral therapy. Stability studies indicated that the optimized formulation remained stable under
accelerated storage conditions. Conclusion: The developed combination transdermal patch of Leflunomide,
Piroxicam, and Methotrexate demonstrated promising physicochemical characteristics, sustained drug release,
improved bioavailability, and formulation stability. The study suggests that the transdermal delivery system may
serve as an effective and patient-friendly alternative for long-term management of Rheumatoid Arthritis