344 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 4O • 35 o • 30 25 o 20 ([ 15 z ,• I0 SYSTEM: Bri•3,•= 2 gm Arlocel'186 = 4 grn n-Tetrodecone = I0 rnl Isoproponol = 3 rnl Woter vorioble. I I I I I O.I 0.2 0.3 0.4 0.5 WATER TO OIL RATIO i I Figure 6. The effect of water-to-oil ratio on the kinematic viscosity of microemulsions. water-to-oil ratio could be attributed to a percolation transition which gives rise to a continuous path through aggregated droplets beyond a critical volume concentration of droplets (33-34). 3. SOLUBILITY OF HYDROCORTISONE IN PHARMACEUTICAL MICROEMULSIONS Solubility of hydrocortisone in isopropanol was determined spectrophotometrically. The maximum solubility obtained by this method (8.5 mg/ml) agreed with the value obtained gravimetrically (8.55 mg/ml). It was observed that the solubility of hydrocorti- sone was greater in isopropanol/water mixtures than in pure isopropanol. The solubility exhibited a maximum when 20% water was present in the alcohol and then

MICROEMULSIONS 345 5 E 4 •L z • 2 z o I SYSTEM: Bri•35,• 2 gm ArleceP'186 = 4 grn n-Pentedecene = I0 rnl Isopropenol = .'.'5 rnl Weter verieble. Frequency = 50-60 Hz i i i I i 0.1 0.2 0.3 0.4 05 WATER TO OIL RATIO Figure 7. The effect of water-to-oil ratio on the conductance of microemulsions. dropped off with further addition of water (Figure 8). The maximum solubility is a result of the polarity of the medium reaching the polarity of the drug (33). The influence of polarity of the medium was further confirmed by the determination of solubility in isopropanol-tetradecane mixtures and glycerol-isopropanol mixtures (Figures 8 and 9). The solubility of the steroid in microemulsions was determined by gravimetric means, since spectrophotometry could not be employed due to strong absorption of the surfactants in the ultraviolet region. As in the model system, the maximum solubility was independent of the water-to-oil ratio within the limits of experimental error (Table V). Also, the solubility was found to be independent of the oil chain length (Table VI). Replacing water by 0.998 NaCI did not change the steroid solubility (Table VI). Thus, as in the model system, the solubility of the steroid in these microemulsions is greater than that in the alcohol on a volume basis of alcohol present per unit volume of the