MICROEMULSIONS 339 Table I Dependence of Solubility of Hydrocortisone on Alcohol and Oil Chain Length in Sodium Stearate Microemulsions at 20øC Max. Solubility of Hydrocortisone System mg/ml Sodium Sodium Sodium Sodium Sodium Sodium Stearate/butanol/hexane Stearate/butanol/decane Stearate/butanol/tetradecane Stearate/pentanol/hexane Stearate/pentanol/decane Stearate/pentanol/tetradecane Sodium Stearate/hexanol/hexane Sodium Stearate/hexanol/decane Sodium Stearate/hexanol/tetradecane Sodium Stearate/heptanol/hexane Sodium Stearate/heptanol/decane Sodium Stearate/heptanol/tetradecane 7.32 7.70 8.70 5.05 6.06 6.3O 4.3O 4.92 5.05 3.53 3.78 3.65 All systems with 1 gram sodium stearate, 8 ml alcohol, 10 ml oil, and 1 ml water. surfactant concentration bring about only slight changes in the maximum solubiliza- tion capacity of the steroid (Table II). With sodium myristate as the surfactant, similar trends were observed. The sodium myristate microemulsions unlike those based on sodium stearate were turbid when prepared due to insoluble impurities present in the surfactant, but became clear when spun in a centrifuge at 5000 rpm for 15-20 minutes. Such clear emulsions were employed for solubility studies. Representative data are tabulated (Table III). Thus, it is evident that the drug solubilization capacity of microemulsions is better than that of pure alcohols on a volume basis of alcohol incorporated in the system. It should be emphasized that other components of microemulsions do not solubilize hydrocorti- sone to any significant extent. It has been reported that the presence of non-ionic surfactants facilitates the dissolution and solubility of water insoluble drugs by incorporation in micelies (27-28). It is felt that in these microemulsions, the drug Table II The Effect of Sodium Stearate Concentration On Solubility of Hydrocortisone in Microemulsions at 20øC System Max. Solubility of Hydrocortisone. mg/ml Sodium Stearate/butanol/tetradecane Sodium Stearate/pentanol/tetradecane Sodium Stearate/hexanol/tetradecane Sodium Stearate/heptanol/tetradecane 8.7* 9.34** 6.30* 7.58** 5.05* 5.68** 3.66' 4.67** *With 1 gram sodium stearate, 8 ml alcohol, 10 ml oil, and 2 ml water. **With 2 gram sodium stearate, 8 ml alcohol, 10 ml oil, and 2 ml water.

340 .JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table III The Effect of Alcohol Chain Length On Solubility of Hydrocortisone in Sodium Myristate Microemulsions at 20øC System Max. Solubility in mg/ml Sodium Myristate/butanol/decane 8.21 Sodium Myristate/butanol/tetradecane 8.83 Sodium Myristate/pentanol/decane 6.56 Sodium Myristate/pentanol/tetradecane 5.80 Sodium Myristate/hexanol/decane 5.30 Sodium Myristate/hexanol/tetradecane 4.97 Sodium Myristate/heptanol/decane 3.80 Sodium Myristate/heptanol/tetradecane 3.66 All systems with 1 gram sodium myristate, 8 ml alcohol, 10 ml oil, and 1 ml water. molecules are predominantly situated at the oil-water interphase with their hydrophilic groups directed towards the water pool. The slight increase in solubility with increase in oil chain length for butanol, pentanol, and hexanol containing microemulsions could perhaps be attributed to the increase in the alcohol/soap molar ratio at the interface as reported by Bansal et al. (30). 2. PREPARATION AND CHARACTERIZATION OF PHARMACEUTICAL MICROEMULSIONS Brij © 35 and Arlacel © 186 were employed as surfactants, and isopropanol was incorporated as the cosurfac'tant in the formulation. The formulation was achieved by mixing the surfactants in suitable proportions, adding oil and isopropanol, and titrating the system against water to clarity with magnetic stirring. We found that the HLB approach was not of much use in the formulation of these microemulsions although it has been reported to be useful in the formulation of macroemulsions. The formulation of a microemulsion was thus an empirical job. Table IV shows the maximum amount Table IV Maximum Solubilization of Water in Pharmaceutical Microemulsions with Various Concentrations of Surfactants Maximum Water Arlacel © 186 in gms Brij © 35 in gms Solubilized in ml 1 5 0 1 4 0 1 3 0 1 2 0 2 4 3.1 2 3 2.0 2 2 1.3 2 1 0.5 3 3 2.5 3 2 2.6 3 1 2.1 4 2 7.0 4 1 4.0 5 1 8.2 6 0 1.4 All systems contain 10 ml n-decane oil and 4 ml isopropanol.