DEVELOPMENT AND EVALUATION OF TRANSDERMAL NANOEMULGEL CONTAINING TERIFLUNOMIDE FOR THE TREATMENT OF RHEUMATOID ARTHRITIS

Akshay Patel* and Bansi Zalavadia

ABSTRACT

The objective of this research work was development and evaluation of transdermal formulation containing teriflunomide for the treatment of rheumatoid arthritis. To bypass first pass metabolism in liver which improves patient compliance with reduced gastrointestinal side effects with transdermal formulation with improved skin permeation. Transdermal nanoemulgel containing teriflunomide were prepared by spontaneous emulsification method with oleic acid as oil and tween 80 and transcutol p as surfactant and co-surfactant. With different ratio of surfactant and co-surfactant ternery phase diagram was obtained. Using 32 design nanoemulsion were optimized and evaluated by zeta potential for stability, and incorporated with hydrogel matrix prepared by xanthan gum as gelling agent. The final emulgel formulation was prepared and evaluated for parameters like viscosity, pH, spreadability, drug content, in vitro diffusion and ex-vivo permeation study. The particle size of all nanoemulsion formulation were observed in nanometer range (150-250nm), PDI (0.1-0.3). Response surface methodology was helped to optimize nanoemulsion formulation, the optimized batch evaluated for zeta potential (-18.2) analysis and selected for nanoemulsion based hydrogel formulation. Nanoemulgel (NEG 1, NEG 2 and NEG 3) were evaluated for pH (5.3±0.2, 5.4±0.2, 5.4±0.3), viscosity (10,321±174.4, 14,475±176.6, 16393±148.3mpa·s), spreadability (43.24±2.18, 36.11±3.40, 22.66±1.87 g.cm/s) and drug content (98.80±0.62, 97.38±1.04, 96.24±0.74 %) accordingly. In-vitro drug diffusion of formulation was done based on release and optimum viscosity NEG 2 evaluated for ex-vivo permeability flux obtained 0.232 mg/cm2/h. and cumulative amount of drug permeated 3.41 mg/cm² (in 24 h).

Keywords: Teriflunomide, Rheumatoid Arthritis, Nanoemulsion, Nanoemulgel, 32 full factorial design, Optimization.