The aim of this study is to formulate and investigate in vitro penetration of  niosome  gels containing essential oil of betel leaf (Piper betle L.) as an anti-acne treatment. The in vitro penetration evaluation was determined using Franz diffusion cell. The preparation of niosome aims to increase the transfollicular penetration and also increase the stability of gels. Betel leaf essential oil extraction was done by steam distillation method and essential oil compounds  identification  used  GC-MS. The niosome formulations made in three kinds of cholesterol and surfactant amount ratio, ie 1:1 (F1), 1:2 (F2)  and 1:3 (F3) (w/w). The niosomes were evaluated which  include the entrapment efficiency  test by HPLC, the particle size test by Particle Size Analyzer, and the vesicle morphology test by Transmission Electron Microscope. The niosomes that had been evaluated, made into gel with 0.5% Carbomer 940 as gelling agent. Niosome gels were evaluated which include organoleptic, pH, viscosity, antibacterial activity against Propionibacterium acnes, and stability for 12 weeks in 3 different storage temperatures, ie room temperature (28±2°C), low temperature (4±2°C), and high temperature (40±2°C).

Keywords: Penetration, Franz diffusion cell, anti-acne treatment, betel leaf, noisome, gel.