Formulation, Evaluation and Optimization of Transdermal Drug Delivery System of Methotrexate Using Different Ratio of Eudragit RLPO / RSPO

Abstract

The present investigation was aimed to development, evaluation and optimization of transdermal preparations capable of administering Methotrexate (MTX), which is at present considered to be most effective for rheumatoid arthritis, more safely than conventional oral preparations while permitting high compliance. Transdermal patches of Methotrexate were prepared by solvent casting method using Eudragit RLPO: Eudragit RSPO in different ratios along with Di butyl -n- phthalate as plasticizer. MTX containing transdermal patches were formulated by using central composite design having 2 independent variables at 3 levels. Independent variables were total amount of polymers (X1 ) and % of Eudragit RSPO (X2 ). The prepared formulations were evaluated for various physicochemical properties like flexibility, thickness, smoothness, weight variation, Tensile Strength, Folding Endurance and Drug Content and was found to be flexible, smooth, uniform thickness and weight, suitable drug content (98 to 99.9 %) and good Folding endurance (> 100). The prepared formulations were also evaluated for in-vitro drug release and Ex-Vivo drug diffusion characteristics. Statistical Optimization carried out for various responses like ‘K’ of zero order, T50% and T80%. Optimized Formulation was found to provide more controlled diffusion of drug. Release kinetics of Optimized Formulation followed zero order drug diffusion. Hence Optimized Transdermal Patch could be a promising delivery system for Methotrexate with sustained release action and improved drug availability.