The aim of the research study was to formulate a novel, biodegradable, injectable in situ gel system of Methotrexate (MTX) in the management of Rheumatoid Arthritis (RA). Varying concentration of Pluronic F-127 (20% and 22% w/v) and xanthan gum (0.2%-0.6% w/v) were used in the development of the formulations. In vitro and in vivo studies were carried out for the prepared MTX in situ gels. The results demonstrated that MTX was uniformly distributed and the in situ gels were sterile and syringeable. The gels showed thermosensitivity and thermoresponsivity dependent on concentration and composition of co-polymers. The optimized formulation exhibited drug release of 95.29% at 132 h. Polymer concentration and composition influenced the release of the drug from the prepared in situ gels. Drug release patterns for the developed gels using various kinetic models was checked and were found to be following non-fickian diffusion mechanism and first-order kinetics. In vivo studies carried on Freunds adjuvant induced monoarthritis in male w istar rats; results showed a significant reduction in the inflammation at the test site. The gels were biocompatible since no inflammation was observed in the synovial membrane. MTX in situ gels could be proposed as an effective delivery system management of RA in near future.
Key words: Rheumatoid Arthritis, Methotrexate, Xanthan gum, Pluronic, Management
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