ROSIN-BASED POLYMER AS CREAM BASE 203 remove any subcutaneous matter and fatty tissues. It was then immersed in phosphate- buffered saline (pH 7.4) at 37øC for 30 minutes for equilibration before use in release studies. EVALUATION OF DRUG RELEASE A Keshary Chien diffusion cell was used for this part of the study (14). Phosphate- buffered saline (10 ml), used as a receptor medium, was placed in the lower part of the diffusion cell. It was placed on a magnetic stirrer with a small magnetic needle placed inside for uniform distribution of the diffusant. The temperature of the cell was main- tained at 37øC + 5øC, by a thermostatically controlled water bath. Isolated rat skin was carefully placed over a 1-cm 2 orifice of the receptor chamber, and precisely weighed formulations were applied to the epidermal side of the mounted skin. Samples (1 ml) were removed from the receptor compartment at regular intervals of one hour, and an equal volume of fresh phosphate-buffered saline was added. Samples were assayed by the colorimetric method of analysis after subsequent dilution. The study was performed for eight hours, and percent release was calculated. STABILITY STUDIES The prepared creams were stored at three different temperatures: room temperature, 40øC, and 55øC, for 50 days using a controlled-temperature oven (Thermonic Labs. Pvt. Ltd.). The parameters of stability assessment were drug content, pH, particle size, conductivity, relative dielectric constant, and viscosity. Dr/ag content, The drug content of the creams were determined by dissolving one gram of the cream in water and estimating the drug by using a U¾ spectrophotometer (Shi- matzu-1602) at 254 nanometers, for diclofenac diethylammonium. The standard graph was prepared by dissolving 50 mg of diclofenac diethylammonium in water. Five mil- liliters of this solution was then diluted to 100 ml, and absorbance of this solution was measured at 254 nanometers. The standard graph was plotted using various dilutions, and the drug content in the creams was calculated from the absorbance of the solutions of prepared creams. Determination ofpH, The pH of 1 g% of the suspension of cream was determined using a pH meter (Hanna Instruments). Particle size determination. The particle size of the prepared creams was determined using a Leitz-Larolux-S-microscope. Three hundred globules were counted using an eyepiece micrometer attached to a 10X eyepiece and with a high power objective of 45X. The eyepiece micrometer was calibrated using a stage micrometer. The average size of a globule in terms of eyepiece micrometer was multiplied by a magnification factor to obtain actual globule size in microns. Conductivity and relative dielectric constant measurement. The conductivity was determined using a digital conductometer (Elico Pvt. Ltd. model CM-180). The relative dielectric constant was determined using a Universal dielectrometer (Type: OH-301, no. 457). The measurement of the relative dielectric constant was carried out by reading the capacitance of a condenser containing the solution of the polymer between the plates. A probe capacitance cell, which could be attached to the dielectrometer through a coaxial

204 JOURNAL OF COSMETIC SCIENCE plug, was used to measure the pF value (capacitance). About 30 ml of polymeric solution was taken into a suitably sized cylinder, and the head of the probe cell was dipped into the solution. Care was exercised to take all the readings at the same temperature and at the same height. All measurements were done at a fixed frequency of 3 mc/S. The conductivity measuring cell lends itself to relative measurement of pF value for com- parison. The recorded pF values were used as such without further reduction and were thus designated relative dielectric constants (relative DEC). The relative DEC for water was found to be 54, whereas the value of DEC is 80. The creams were allowed to equilibrate to room temperature before the readings were taken. Viscosity measurement. The viscosity study was done by a Brookfield synchro-lectic vis- cometer, using the method as specified by the manufacturer. RESULTS AND DISCUSSION It was observed that the creams show good spreadability and homogeneity. EVALUATION OF DRUG RELEASE Figure 1 shows the percent release of diclofenac diethylammonium from various creams in the receptor medium across the rat skin. Cream containing polymer 2 showed better release of the drug for the first two hours than did the marketed cream. The overall release was greater for the marketed preparation after two hours. The cream containing Tween 60, however, showed a poor release pattern as compared to the marketed prepa- ration and creams containing polymer 2. The cream containing polymer 2 showed the 16 14 = • 10 0 I [ I I I 4 õ 6 7 8 Time (Hours} -•- RM + RT -•-- R2 Figure 1. Comparison of in vitro release profile of diclofenac diethylammonium from various cream bases with marketed preparation using Keshary Chien diffusion cell. RM: marketed cream. RT: cream with Tween 60. R2: cream with polymer 2.