24 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS The equation for this type of curve was found to be of the form y--b c+Klog-- -- x Eq. 2. a-y where c = constant, b = constant, a = constant, K = constant, x = W/W concentration of water in base (%), and y = diffusion distance in two hours (mm.). The constants a and b were found graphically by extrapolation of the curve to x = 100 and x = 0 respectively. The values of y at these points were used in each case. The value of c was found to be the value of x at the inflection point of the curve (where y = } (a -- b) + b). The value of K was found by the method of averages. 8 The data obtained from ointments No. 1, 2, 3, 9 and 10 were not used because an extremely small variation in the experimental readings of points near the limits of the curve made an overwhelming variation in the value of K. By evaluation of the constants in Equation No. 2, Equation 3 was derived: y -- 2.5 37.4+12.1 log 8-8--y--X' Eq. 3. Although the slope ot the curve is relatively high near the inflection point, i t is not infinity. This indicates that the phase reversal is not a step change, but a gradient change. It has been generally accepted that emulsions con- taining water and oil are either of the water-in-oil or oil-in-water type. If we assume that the diffusion rate of sulphathiazole from an emulsion is an indication of the emulsion type, it appears that emulsions can possess properties which place them somewhere between these two classes. There may be degrees of aqueousness or degrees of oleagenousness of the external or internal phase. In testing for emulsion type using an oil-soluble dye,' it was found that the phase reversal point corresponded to the inflection point on the curve. In Table 2, all ointments whose bases contained 41.4 per cent or more of water were of the oil-in-water type, and all ointments containing 33.1 per cent or less of water were of the water-in-oil type. The inflection point on the curve was between these two concentrations of water at 37.4 per cent. Comparison of the Method.--Lockie and Sprowls,'" using the agar gel method developed by Waud and Ramsay, 4 determined that a mathematical relationship existed between the diffusion distance and the period of time that the ointment was in contact with the agar gel. The equation for this relationship is as follows:

WATER AND OIL RATIO OF COLD CREAM 25 y•= kx Eq. 4. where y ---- the diffusion distance in mm., x •- the period of time in hours, and k = a constant which varies with the ointment base used. In this equation, the value of k is an indication of the diffusion rate in each case. The ointments listed in Table 3 were prepared as described by Lockie and Sprowls. 2 All ointments contained l0 per cent sulphathiazole by weight. TABLE 3 COMPARISON OF DIFFUSION OF THE CHROMATOGRAPHIC AND THE AGAR GEL METHODS Ointment Base Carbowax Base Vanishing Cream B Petrolatum Petrolatum with 30% water Beeler's Base Aerosol OT Emulsion Diffusion in mm. by Filter Paper Method 3.8 8'5 O. O. 7.8 3.5 Coefficient of x 13'3 10'6 0.! 0.! 11.0 13.3 f A trace of diffusion was actually reported. All recorded diffusion distances are averages of two determinations. A statistical correlation can be obtained using the following equation:" ,,Zxy -(2:x) (2:y) r= Eq. 5. 'V' (nZ'x • -- (,.Sx•) (n,.Sy• -- (Z'y)'•) where r •- correlation coefficient, n -• number of samples, x == values obtained by one method, and y =: values obtained by other method. The value obtained for r is 0-7. Because of the small number of samples, the value of r should not be considered as an exact quantitative value, but merely an indication that there is a rather high correlation between the two methods. SUMMARY 1. It has been further established that sulphathiazole diffuses more rapidly from oil-in-water than water-in-oil type emulsion bases. 2. A chromatographic method for testing diffusion rates of drugs from ointment bases, using moistened filter paper as a diffusion media, has been described in detail. 3. On the basis of this work, the phase reversal in cold cream type emul- sions is a gradient change rather than a step change.