19, 18- 16- 14- 4- I 2- I 0 I E 12 E z I0 0 0 o 8 0 6 SPECTROPHOTOMETRIC X. = 243nm I I I I I I I I I J • I 2 3 4 5 6 7 8 9 I0 II 12 13 14 PERCENTAGE GLYCEROL (v/v) Figure 9. Solubility of hydrocortisone in isopropanol-glycerol mixtures of various compositions. Table V Maximum Solubility of Hydrocortisone in n-Decane Microemulsions at Various Water-to-Oil Ratios Water-to-Oil Ratio Max. Solubility in mg/ml 0.1 8.3o 0.2 8.51 o.3 6.85 o.4 7.35 0.5 7.10 System: n-Decane = 10 ml Isopropanol - 4 ml Arlacel © 186 = 4 gm Brij © 35 = 2 gm Temperature = 20øC 347

348 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table VI Maximum Solubility of Hydrocortisone in Microemulsions with Various Oils Oil Max. Solubility in mg/ml n-Octane 8.2 n-Tetradecane 8.5,8.3* n-Pentadecane 7.8 n-Hexadecane 8.1 System: oil = 10 ml, Isopropanol = 3.5 ml, Arlacel © 186 = 4 gm, Brij © 35 = 2 gm, Water = 3 ml, Temperature = 20øC. *With 3 ml of 0.9% NaCl. uses and applications of microemulsions (36-43), they can also serve as vehicles for oil soluble, water soluble, and interphase soluble species for cosmetic and pharmaceutical formulations. Formulations of microemulsions with low concentrations of the surfactants and pharmaceutically acceptable alcohols and oils are under way. The kinetics and mechanism of dissolution, solubilization, as well as the stability of certain cortisteroids in such microemulsions, will be reported elsewhere. CONCLUSIONS 1. The solubility of hydrocortisone was found to decrease with an increase in chain length of alcohols, the solubility being the maximum in n-butanol and minimum in n-heptanol. 2. In conventional microemulsions, the solubility of hydrocortisone was found to be independent of the water-to-oil ratio. An increase in oil chain length did not have any significant effect on the solubility of the steroid. 3. The solubility of hydrocortisone was adversely affected by increasing the chain length of alcohol in the microemulsion system, as in the case of pure alcohols. The solubility was comparable to that in pure alcohols. 4. The water solubilization capacity of pharmaceutical microemulsions increased with an increase in concentration of the oil soluble surfactant Arlacel © 186. The water solubilization was maximum at 5:1 (wt/wt) ratio of surfactants Arlacel © 186 and Brij © 35. Either Brij © 35 or Arlacel © 186 alone in combination with oil and isopropanol was not very effective in solubilizing water. 5. Replacing water with 0.9% NaCI in the system gave rise to viscous birefringent systems with dodecane and tetradecane as oils. With octane and decane as oils this behavior was not observed, and the transition was similar to that observed with water. 6. Viscosity data indicated that the pharmaceutical microemulsions were of the water-in-oil type. 7. Solubility of hydrocortisone in pharmaceutical microemulsions was comparable to that in isopropanol. On a volume basis of alcohol incorporated per unit volume of the microemulsion, the solubility of hydrocortisone was found to be six fold higher