20 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS a R. Schnurmann, "l•,tude spectroscopique de la stabilitd photochimique d'huiles de paraffine mddicinales." Journal de Physique, 11i, 503, 1954. ' R. Schnurmann, "The 'Group A' compounds in medicinal liquid paraffin."-- Transactions of the 27th International Congress of Industrial Chemistry, Brussels 1954 THE EFFECT OF VARIATION OF THE WATER AND OIL RATIO ON THE DIFFUSION RATE OF SULPHATHIAZOLE FROM COLD CREAM TYPE OINTMENT BASES AUBERT CORAN* and C. LEE HUYCKi The authors study the effect of varying the phase ratio of cold cream con- raining sulphathiazole. They find that reversal of the external phase is a gradual change and describe two methods for determining the rate of diffusion of the drng from the cream. IT WAS recently established • that cold cream type ointments containing mineral oil, beeswax, borax, and water may be either of the oil-in-water or water-in-oil type, depending upon their oil and water concentration. It was shown •,• that sulphathiazole diffuses more rapidly from oil-in-water type emulsions than from the water-in-oil type. The purpose of this investigation is to show the change in the rate of diffusion of sulphathiazole from this type of base as the water and oil concentrations are changed and to compare two methods of testing the diffusion of sulphathiazo]e from ointment bases. In vitro studies of diffusion rates of drugs from ointment_bases have been &X•..e_nsively conducted by the use of the agar gel method which was developed by Waud and Ramsay.' This method employed an agar 'g• •cø•[•[ihing an i•dicator. The ointment being tested was placed on top of the gel which was contained in a test tube. Measurements of the extent of diffusion was based upon the distance from the top of the gel to the bottom of the indicated area. Other methods 5'6 have shown the extent of diffusion into saline solutions, blood-serum, and water. The method used here was taken from a recent note7 which presented a new method of determining the extent of diffusion of drugs from various ointment bases. This method employed a piece of filter paper moistened with indicator solution. The ointment was placed in the centre of the filter paper in a small hollow cylinder open at both ends. Determinations of the diffusion rates were made by measuring the distance from the outer edge of the ointment to the outer edge of the indicated ring on the filter paper. * Graduate Assistant in Chemistry, St. Louis College of Pharmacy & Allied Sciences, St. Louis 10, Mo. t Professor Industrial Pharmacy, St. Louis College of Pharmacy & Allied Sciences, St. Louis 10, Mo.

WATER AND OIL RATIO OF COLD CREAM 21 EXPERIMENTAL Cold cream type ointment bases were prepared by formulae given in Table 1. TABLE 1 CM. INGREDIENTS OF COLD CREAM TYPE OINTMENT BASES Ointment Number 1 2 3 4 5 6 7 8 9 lO Borax U.S.P. 0'48 0-48 0'48 0'48 0'48 0'48 0'48 0'48 0'48 0'48 White Wax U.S.P. 8.3 8.3 8.3 8.3 8.3 8.3 8.3 8.3 8.3 8.3 Liq. Pet. Oil U.S.P. 8-3 16.6 25.0 33.3 41.6 50.0 58-3 66.6 75.0 83.3 Dist. Water U.S.P. 83 '3 75-0 66'6 58'3 50.0 41-6 33'3 25'0 16'6 8-3 In each case the oil and wax were melted together and heated to 65 ø C. The borax was dissolved in distilled water at 65 ø C. The aqueous phase was then gradually added to the oil phase with constant agitation. The agitation was accomplished by means of a laboratory stirrer fitted with a circular type stirring blade having a diameter of four cm. The rate of rotation of the stirring blade was approximately 1,500 r.p.m. The agitation was continued until the ointment base had cooled to about 35 ø C. Ointments of sulphathiazole were prepared from each base according to the following formula: Sulphathiazole, U.S.P. 5.0 gm. Cold Cream Base 45.0 gm. To make 50.0 gm. The sulphathiazole was levigated with about five gm. of the base on an ointment tile by means of a spatula. The rest of the base was then incor- porated by geometric dilution. The type of emulsion (Table 2) in each case was determined • after the incorporation of the sulphathiazole. This was accomplished by spreading the ointment being tested on a smooth surface and sprinkling it with a few grains of the oil soluble Sudan Yellow. If the emulsion was of the water-in- oil type, the dye could be seen diffusing into the ointment. A magnifying glass was used to make this observation. Ten pieces of Whatman, No. 40 filter paper, seven cm. in diameter, were selected on the basis of their weight. Each of the selected pieces of filter paper weighed 340 .-Jr 5 mg. The filter papers were numbered from 1 to 10. Each of the numbers corresponded to one of the sulphath!azole ointments.