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
346 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 40 36 ... 28 ,,, 24 o 0:20 o o 12 ? / 0 I0 20 30 40 50 60 70 80 9,0 I00 PERCENTAGE ISOPROPANOL (v/v) Figure 8. Solubility of hydrocortisone in isopropanol-water mixtures (A), and isopropanol-tetradecane mixtures (B). microemulsion. Since the drug solubility as before was found to be independent of the water-to-oil ratio as well as the chain length of the oil employed, the mechanism of solubilization could be the same as in the model system. All microemulsions were found to be stable up to a temperature of 70øC. Spinning the microemulsions in a centrifuge at 5000 rpm for two hours did not induce phase separation. Incorporation of 2 ml of carnation mineral oil along the hexadecane oil was found to yield a microemulsion which did not undergo phase separation when kept at 40øC for more than two months, though the mineral oil alone failed to give any microemulsion. Thus, it appears that when judiciously formulated, microemulsions are potential vehicles for topical applications. In contrast to macroemulsions, they are clear, isotropic, and stable. Because of the small particle size, the total interfacial area is much greater in microemulsions than in macroemulsions. Thus, besides the several known
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