Formulation Development of Nicotinamide Microemulsions Using Natural Oils as Oil Phase

Abstract

Concerning the conservation of ecosystem, biodegradable and environmental friendly chemicals have been chosen to formulate as green microemulsions (MEs). The objective of this research was to investigate phase behavior of nonionic surfactants with natural oils on formation of green MEs. In this study, MEs were formulated from olive oil or virgin coconut oil with various ratios of surfactant mixture (Smix) between polyoxyethylene (20) sorbitan monooleate (Tween 80) and sorbitan monooleate (Span 80). The formulation scanning was carried out based on hydrophilic lipophilic deviation (HLD) concept followed by titration method. From the obtained pseudotenary phase diagrams, surfactant:cosurfactant (S:COS) ratios of 0.6:0.4 and 0.7:0.3 were chosen as Smix. The compositions of blank MES were 45% w/w of oil, 50% w/w of Smix and 5% w/w of water. The visual and technical characterization of formulations indicated that all MEs were water-in-oil (w/o) type. After accelerating stability test, 3% w/w of nicotinamide was added to blank MES to obtain MEO1-N, MEO2-N, MEC1-N and MEC2-N. They were characterized as w/o MEs. Afterward, samples were kept at 4°C, room temperature (28 ± 2°C) and 45°C for three months to study physical and chemical stabilities. MEO2-N got phase separation since the first month of storage at all conditions due to enlarged entropy. The drug remaining content was assayed by HPLC method and more than 90% of active was detected in MEO1-N, MEC1-N and MEC2- N kept at 4°C and room temperature. High temperature, 45°C, caused discoloration in all formulations. The in vitro release profiles of MEO1-N and MEC1-N were compared with 3% w/w nicotinamide solution (NCT sol). After 12 h, NCT sol reached a plateau while MEO1-N and MEC1-N provided the sustained release profiles which were best fitted to the Higuchi model. The release rate of MEO1-N was higher than MEC1-N because of the board intermolecular area of fatty acid chain allowing nicotinamide to diffuse better. The in vitro release kinetics of after three months stored MEs also followed the Higuchi model and the release rate was significantly different to freshly prepared MEs (p <0.05, t-test). The current observation revealed that not only HLB but also the degree of saturation of fatty acids, water-to-lipid ratio and S:COS ratio influenced the formation of MES type and stability. The in vitro release rate was affected by the oil type when the same Smix was applied. These natural oil microemulsions were promising as nanocarriers of nicotinamide. Moreover, they could be further observed for incorporation of other active ingredients and effectiveness of active delivery to the skin.