MICROEMULSIONS 337 emulsifiers, alternate terminology has been proposed by various workers (20-25). A survey of pharmaceutical literature revealed that microemulsions have not been explored at all as vehicles for drug delivery in spite of their unique properties. Thus, the present study was undertaken to explore the potential of microemulsions as drug delivery systems, particularly in the area of topical preparations. The dissolution, solubilization, and stability of hydrocortisone in various vehicles have been reported by previous workers (26-29). In this paper we report some of our findings on the solubilization of hydrocortisone in conventional microemulsions as well as in micro- emulsions formulated with pharmaceutically acceptable surfactants. EXPERIMENTAL The microemulsions were prepared by mixing the surfactant(s), alcohol, hydrocarbon oil, and water in suitable proportions and stirring the mixture to clarity with a magnetic stirrer. Sodium myristate was a K & K laboratories product (Practical grade), and sodium stearate was obtained from ICN Pharmaceutical Company. Both Brij © 35 and Arlacel © 186 were purchased from ICI Americas Inc. Alcohols (Fisher Scientific Company) and oils (Chemical Samples Company or Phillips Petroleum Company) of 99 mol. % purity were used. Micronised hydrocortisone was a gift from Alcon Pharmaceu- tical Laboratories. Solubility studies in microemulsions based on sodium stearate and sodium myristate as surfactants were carried out by stirring excess of the solid steroid in the solvent at room temperature, centrifuging till clear, and assaying the resulting solution spectrophotometrically at 243 nm. With Brig © 35 and Arlacel © 186 as the surfactants, the spectrophotometric method could not be employed since the surfactants absorbed strongly in the ultraviolet region. Therefore, a gravimetric method was employed. This involved stirring a known excess of the drug in a known volume of the microemulsion and filtering the resulting solution quantitatively through a sintered medium porosity crucible. A known excess of the drug was accurately weighed into a known volume of the microemulsion and was allowed to equilibrate for a period of three hours while the solution was kept stirred magnetically using a teflon coated magnetic bar. After equilibration, the solution was filtered quantitatively through a medium porosity sintered crucible using an aspirator. The drug remaining in the crucible was washed free of the emulsion several times with distilled water and the corresponding oil, and dried at 70øC to constant weight. From the weight of the drug remaining in the crucible, the amount dissolved was computed. The accuracy of the gravimetric method was checked in the case of sodium stearate microemulsions wherein solubility of hydrocortisone could be determined spectrophotometrically. The accuracy of the method was found to be within _+0.5%. Viscosity measurements were carried out in a Cannon-Fenske viscometer at room temperature, while the conductivity data were obtained using a Beckman conductivity bridge. RESULTS AND DISCUSSION 1. SOLUBILIZATION OF HYDROCORTISONE IN MICROEMULSIONS BASED ON SODIUM STEARATE AND SODIUM MYRISTATE AS SURFACTANTS The maximum solubilities of hydrocortisone in various pure alcohols are given in Figure 2. The solubility of hydrocortisone in water has been reported to be 7.43 x 10 -3

338 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS E WATER TO OIL RATIO 0 O, I O. 2 0.3 0.4 O. 5 0.6 MICROE MULSION COMPOSITION Sodium Steorote Igm n-Pentonol 8 ml n-Tetrodecone I0 ml A= Solubility in Alcohol B= Solubility in Microemulsions o i I I C 4 C 5 C 6 C 7 ALCOHOL CHAIN LENGTH Figure 2. The solubility of hydrocortisone in alcohols of various chain lengths (A), and in microemul- sions as a function of water-to-oil ratio (B). mol. dm -3 at 20øC (27). It is practically insoluble in hydrocarbon oils. The solubility of hydrocortisone in microemulsions based on sodium stearate, various alcohols and oils at a water-to-oil ratio of 0.10 are given in Table I. It can be seen that the solubility is maximum with n-butanol and minimum with n-heptanol (Figure 2, Line A). Consider- ing the volume fraction of alcohols present in these systems, it may be noted that the solubility of the steroid in unit volume of the microemulsion is at least twice greater than that in pure alcohols. Though an increase in oil chain length results in an increase in the solubility of the drug, the effect is much less marked than when the chain length of alcohols is varied. An increase in water-to-oil ratios is without any effect on the solubilization capacity of these microemulsions (Figure 2, Line B). Also, changes in