Formulation andEvaluation of Aceclofenac and Quercetin Nanoemulsion-Based Gel Against Rheumatoid Arthritis.

Abstract

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory, T cell-mediated autoimmune disorder which commonly affects the tiny joints of the hands and feet. OBJECTIVES: To develop and evaluate novel topical gel containing combinatorial aceclofenac (ACF) and quercetin (QCT) nanoemulsion (NE) for management of RA. METHODS: NE components (oil, surfactant, and cosurfactant) were selected based on solubility. Pseudo ternary phase diagrams were constructed using titration method. Carbopol bases were screened to produce NE-gel. Drug loaded NE-gels were characterized for transmission electron microscopy and in-vitro drug release. Further evaluated for ex-vivo drug release, retention-permeation studies, in-vivo studies using Wistar rat model. RESULTS: Optimized NE showed approximate globule size 79nm, zeta potential of -28.1 &#xb1; 1.20 mV and polydispersity index 0.22. The NE-gel showed in-vitro drug release of ACF=75.56 &#xb1; 0.318% and QCT=74.72 &#xb1; 0.715% after 12h, depicting sustained zero order release kinetics in contrast to marketed gel (release of ACF=95.33 &#xb1; 0.449% after 9h). Ex-vivo study on porcine ear skin revealed improved permeation and minimum retention. In-vivo studies showed 50.89% reduction in paw volume (p<0.0001) with better anti-arthritic effects.&#x2009;&#x2009;. CONCLUSION: The study substantiated combinatorial NE-gel formulation with advanced permeation characteristics which can be an efficient alternative for topical delivery in RA.