j. Soc. Cosmet. ½hem., 34, 335-350 (November 1983) Microemulsions: Evolving technology for cosmetic applications A JAYAKRISHNAN, K. KALAIARASI, and D. O. SHAH, Departments of Chemical Engineering and Anesthesiology, University of Florida, Gainesville, FL 32611. Received June 28, 1982. Presented at the Society of Cosmetic Chemists Annual Scientific Meeting, New York, NY, December 10-11, 1981. Synopsis The solubilization of hydrocortisone by microemulsions based on the combination of sodium stearate and sodium myristate with various alcohols and hydrocarbon oils was investigated by spectroscopic means at room temperature. The alcohols employed were n-butanol, n-pentanol, n-hexanol, and n-heptanol. The oils ranged from n-hexane (C6) to n-hexadecane (C•6). It was observed that an increase in chain length of alcohols affected the solubility adversely. Changes in surfactant concentration, oil chain length, or water-to-oil ratios in the microemulsions did not have any significant effect on the solubility of the steroid. The solubilization capacity of the microemulsions was comparable to that of pure alcohols. The formulation of a microemulsion using pharmaceutically acceptable surfactants and hexadecane oil has been achieved. Brij © 35 and Arlacel © 186 were employed as surfactants, while isopropanol was incorporated as the cosurfactant. The microemulsion was stable upto 70øC without undergoing phase separation. Viscosity data suggested that the microemulsion obtained was the water-in-oil type. Electrical conductivity measurements were interpreted in terms of the percolation theory of charge transport. The solubility of hydrocortisone in the system was determined by gravimetric means and was found to be much greater than in isopropanol on a volume basis of alcohol incorporated in the system. As observed in the case of sodium stearate microemulsions, the solubilization capacity was independent of the oil chain length and water-to-oil ratios in these microemulsions. Replacing water by 0.9% NaCI solution did not affect the solubility of hydrocortisone in microemulsions. Possible applications of microemulsions in skin care and cosmetic areas are mentioned. INTRODUCTION Drug efficacy can be severely limited by poor solubility in suitable vehicles (1). When small amounts of the drug are to be delivered in accurate dosage forms, thermody- namic stability of the molecules in solutions as opposed to thermodynamic instability in suspensions or dispersions becomes an important criterion. Optimization of solubility is a problem in drug formulations in solutions because drug design does not generally take into account a particular level of solubility. Surfactant solubilization is one of the most widely employed techniques for solubilizing water insoluble drugs. Though considerable attention has been focused in this area in recent years, there has been no major advance in predicting the solubility of drugs in micelies of a given surfactant. There are only a few marketed products which could be corisidered to be 335

336 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS isotropic solutions of the drug and surfactant (2). A limiting factor in the use of surfactant solubilizers as effective formulation aids is the finite capacity of the micelies for the drug and the stability of the formulation. Surfactant solubilization has advantages. In the micelie, the reactivity of the solute might be different because of the orientation and proximity of the drug molecu/les. The solute may be protected from attacking species such as hydrogen or hydroxyl ions (3). The ability of the miceliar phase to alter the transport properties of the drug is another advantage in surfactant formulations. Emulsions are widely used in pharmaceutical, cosmetic, and skincare products since they often possess certain advantages not observed when products are formulated in other dosage forms. Emulsification has been widely used in the preparation of dermatological creams and lotions since it facilitates the penetration of the drug into the skin (4). The potency of topical steroids depends on the vehicles used (5). A problem with conventional emulsions is their instability. In general, the droplets in a conventional emulsion have diameters ranging from 0.2 to 50/am. Microemulsions are much more stable systems with droplet size ranging from 100-1000/•k. Also, they are optically clear they are formed spontaneously without the aid of high shear equipment. They are stabilized with the combination of an ionic surfactant and a hydrophobic cosurfactant, commonly an alcohol of medium chain length, or with a non-ionic surfactant of optimum HLB (7). Figure 1 schematically illustrates the structure of WATER-IN-OIL OIL-IN-WATER H20 Figure 1. A schematic representation of the structure of water-in-oil and oil-in-water type microemul- sions in relation to the orientation of the surfactant and cosurfactant molecules. water-in-oil and oil-in-water microemulsions and the orientation of the surfactant and cosurfactant molecules at the interface. Ever since their introduction in industry (8) and in the scientific world (9), microemulsions have received considerable attention because of their application in various fields of science and technology (10). The structure and properties of microemulsions were investigated by Schulman et al. (11-14), who employed various techniques such as light scattering, x-ray diffraction, electron microscopy, ultracentrifugation, electrical conductivity, and viscometry. The formation and physical properties of microemulsions are influenced by the alkyl chain length of alcohol and hydrocarbons (15-19). Though microemulsion is the most widely used term for describing isotropic, clear, low viscosity dispersions of oil, water, and