Injectable in situ gel of methotrexate for rheumatoid arthritis: Development, in vitro and in vivo evaluation

ABSTRACT

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 studieswere carried out for the prepared MTX in situ gels. The results demonstrated that MTX was uniformly distributed andthe in situ gels were sterile and syringeable. The gels showed thermosensitivity and thermoresponsivity dependenton concentration and composition of co-polymers. The optimized formulation exhibited drug release of 95.29% at132 hours by non-fickian diffusion mechanism. Polymer concentration and composition influenced the release of thedrug from the prepared in situ gels. In vivo studies carried on Freund’s adjuvant-induced monoarthritis in male Wistarrats; results showed a significant reduction in the inflammation at the test site. The gels were biocompatible since noinflammation was observed in the synovial membrane. MTX in situ gels could be proposed as an effective deliverysystem management of RA in near future.