331 Application of Reverse Micelles in Cosmetic Formulations HA Hyaluronic acid HLB Hydrophilic lipophilic balance IL Ionic liquid IPM Isopropyl myristate ML Methyl laurate MO Monoolein PC Phosphatidylcholine SC Stratum corneum SURFACTANT Surfactants are one of the main components present in the mixture system aimed to form micelles. Surfactants are amphiphilic molecules that consist of both a hydrophobic tail and a hydrophilic head. The hydrophobic tail repels water or polar solvents while the hydrophilic head attracts them. The hydrophobic tail is made up of linear or branched alkyl chain lengths with 6 to 30 carbon atoms (6, 7). In general, surfactant molecules in a solvent will align themselves near the surface, or interfacial area, and reduce the surface or interfacial tension. The addition of surfactants into an oil and water mixture decreases the surface tension between the oil and water phases (8). Reduction of surface or interfacial tension then leads to micellization (9). This characteristic is exploited to greatly enhance the solubility of various molecules in aqueous or organic solvents. Surfactants can be classified as anionic, cationic, non-ionic, and zwitterionic according to the charge of their hydrophilic head groups (7). The charge on the surfactant head group determines the net charge of the micelles formed. It also affects the type and strength of interactions between the surfactant molecules and the solutes. In general, attractive electrostatic interactions are the main driving forces for the encapsulation of active compounds into reverse micelles. Nonetheless, hydrophobic interactions and hydrogen bonds also contribute to the encapsulation of active compounds. Some of the surfactants commonly used to form reverse micelles are anionic AOT and cationic CTAB. Zwitterionic surfactants may have a net positive, negative, or neutral charge depending on surrounding pH value, although they generally have a neutral charge. Lecithin is a commonly used zwitterionic surfactant in cosmetic formulations. Non-ionic surfactants are rarely used alone in reverse micellar systems due to their low encapsulation efficiency. However, their weaker interactions are beneficial in providing a milder environment for the better protection of the active ingredients. They are usually used together with ionic surfactants to form mixed reverse micelles. Some commonly used non-ionic surfactants are the Span series and Tween series. Surfactants have significant effects on the skin, such as altering the skin structure and allowing for the penetration of active ingredients. In order to maintain healthy skin or to avoid any clinical skin conditions, it is important to maintain the nature of the skin structure (10). Therefore, selection of suitable surfactants for the use in cosmetic formulations is crucial. The surfactants selected must not be skin sensitizers, irritants, or cause skin allergies. Sugar-based surfactants are recently applied in cosmetic products (11). These surfactants are milder to the skin while having good surfactant properties. Surface active ionic liquid (IL) has also gained increasing interest in cosmetic formulations. An

332 JOURNAL OF COSMETIC SCIENCE advantage of using surface active IL is that they can be designed to form micellar systems with the desired properties. In an effort to find more sustainable and environmentally friendly surfactants, researchers have studied the micellization of several biosurfactants. These biosurfactants are obtained from various natural sources such as microorganisms and plants. Some biosurfactants that can form reverse micelles are sophorolipids and rhamnolipids. HYDROPHILIC AND LIPOPHILIC BALANCE (HLB) HLB is an important parameter that determines the tendency of a surfactant to form normal micelle or reverse micelle (12). HLB of a surfactant depends on the hydrophobicity and hydrophilicity of the surfactant (13). It is described by a numerical scale ranging from 0 to 20, and relates to the ratio between the molecular weight of hydrophilic part of surfactant molecule to its total molecular weight. For non-ionic surfactants, HLB value of 0 means nonpolar and 20 means polar soluble. The HLB can be applied to ionic surfactants with a scale up to 50. The HLB of surfactants aimed to form reverse micelles or water-in- oil microemulsion has a value between 3 and 6. On the other hand, HLB of surfactants for the formation of micelles or oil-in-water microemulsion has a value between 8 and 18 (14). CRITICAL MICELLE CONCENTRATION (CMC) At low concentration, surfactant molecules exist as monomers in a solution. When the surfactant concentration in a solution is increased to a certain value, micelles or reverse micelles start to form spontaneously. This concentration is known as CMC. Reverse micelles formed above CMC are thermodynamically stable (15). Surface tension and conductivity measurement are common techniques used to determine the CMC of a surfactant solution. The procedures involve measuring the surface tension or the conductivity of a solution containing an increasing amount of surfactant and making a plot of the measured value. CMC of the system can be identified at the points where abrupt change in the measured values is observed. Another method utilizing solubilization of 7, 7, 8, 8-tetracyanoquinodimethane is also used to determine the CMC of a surfactant solution where rapid change in the color of dye occurs when CMC is reached (16, 17). CMC value depends on several factors such as the type of surfactant, temperature, pH, and ionic strength (7, 16). Typical CMC of commonly used surfactants are between 10−4 mol/L and 10−2 mol/L (11). SELF-ASSEMBLY When surfactant concentration in a solvent reaches their CMC value, the isolated surfactant molecules will spontaneously arrange themselves into ordered structures. The interactions involved during the self-assembly process are Coulomb interaction, hydrophobic interaction, hydrogen bonds, and coordination bonds (18). The self-assembly process is simple and requires only low energy input, such as stirring. Thus, micellar systems have gained interest as carriers for active compounds because of its ease of production and economical advantage (8). Surfactant concentration above their CMC should be used to ensure the formation of functional micelles or reverse micelles.