ABSTRACT Kai, Noviyanti. 2019. The Effect of the Tween-80 Concentration as an Edge Activator on the Characteristics and Diffusion Rate of Diclofenac Sodium Transfersomes. Undergraduate Thesis. Department of Pharmacy, Faculty of Sports and Health, Universitas Negeri Gorontalo. Principal Supervisor: Nur Ain Thomas, S.Si., M.Si., Apt. Co-supervisor: Moh. Adam Mustapa, S.Si., M.Sc. Diclofenac sodium is a non-steroidal anti-inflammatory drug that works by inhibiting the enzyme cyclooxygenase. Orally administered diclofenac sodium causes gastrointestinal and cardiovascular disorders, and 50% of the patients experience First Pass Effect. Transfersom is a transdermal delivery system consisting of phospholipids and edge activators. Transfersom increases the size of the stratum corneum lipid barrier pores, then enters the skin through the drive of the trans-barrier motion and squeezes itself to follow the lipid barrier pore size. The purpose of this study is to determine the effect of the tween-80 concentration as an edge activator on the characteristics and diffusion rate of diclofenac sodium transfersom. Transferom preparation used the vortex-sonication method which was made in five formulae with variations in the concentration ratio of phosphatidylcholine and tween-80 (95:05, 90:10, 85:15, 80:20, and 75:25). Proceeding this stage was the evaluation of morphological observations, entrapment efficiency, particle size, and diffusion rate. The results show that all five formulae have different morphological forms. Fl entrapment efficiency is 92.83%, F2 93.04%, F3 93.67, F492.36%, and F5 91.36%, and has a particle size of 617 nm. The penetration test shows formula 3 (85:15) has a higher diffusion rate than the other four formulas, namely 36.67 ug/cm2/hour. The results of statistical tests using One-Way ANOVA finds a significant effect (p-value 0.01) of the edge activator concentration on the diffusion rate of diclofenac sodium transfersom. Keywords: Transfersomes, Diclofenac Sodium, Edge Activator, Transdermal viii