POLYETHYLENE GLYCOL-8/SMDI COPOLYMER 141 A. SUBSATURATED 0.016 0.012 0.008 0.004 0.000 1.2 i i i i 2 4 6 8 Time (Hours) B. SATURATED 10 • 0.6- 0.4- "• 0.2- 0.0 0 2 4 6 8 Time (Hours) lO Figure 4. Effect of PP-15 on the permeation of salicylic acid from subsaturated and saturated solutions through pig skin. A: O, Control-0.1% SA O, 3% PP-15-0.1% SA. B: O, Control-0.5% SA [•, control- 2.0% SA O, 3% PP-15-0.5% SA l, 3% PP-15-2.0% SA. EFFECT OF THE IONIC STRENGTH OF THE FORMULATION ON THE EFFICACY OF PP-15 The results obtained for the four formulations tested are plotted in Figure 5. The permeation of SA from all formulations was linear with time after approximately a two-hour lag time. The rates of permeation were 2.37 x 10 -3, 1.13 x 10 -3, 1.14 x 10 -3, and 1.03 x 10 -3 mg/cm2/hour for the control, PP~15 without salts, PP-15 with 0.1 M sodium chloride, and PP-15 with 0.1 M calcium chloride, respectively. The similarity in flux values indicated that the ionic strength of the solution did not influence the effect of PP-15.
142 JOURNAL OF COSMETIC SCIENCE 0.018 0.016 0.014 0.012 o.olo 0.008 0.006 0.004 0.002 0.000 i i i 0 2 4 6 8 10 Time (Hours) Figure 5. Effect of ionic strength on the efficacy of PP-15 in 0.1% w/w salicylic acid formulations. ¸, Control O, 3% PP-15 I, 3% PP-15 + 0.1M NaC1 &, 3% PP-15 + 0.1 M CaC12. EFFECT OF PP-15 ON THE APPARENT SOLUBILITY OF SA The addition of 1%, 2%, 3%, 6%, and 10% w/w PP-15 to the formula increased SA apparent solubility from 0.00113 (control) to 0.00159, 0.00244, 0.00311, 0.00614, and 0.00891 gm/ml, respectively. These results are presented in Figure 6. The increase in apparent solubility was linear with the amount of PP-15 added. The addition of 3% PP-15 increased the apparent solubility 2.8 times. DRUG/POLYMER BINDING A plot of the fraction of drug bound as a function of drug concentration is displayed in Figure 7. In the case of PP-15, the data showed that the fraction of SA bound (= 0.55) did not change markedly throughout the range of concentrations studied. It was also found that LA did not bind to PP-15 significantly. EFFECT OF SA AND LA ON THE CLOUD POINT OF PP-15 The effect of the drug concentration on the cloud point of PP-15 is displayed in Figure 8. An increase in the concentration of SA decreased the cloud point of PP-15. This decrease was linear with concentration. It was also found that the presence of LA to a level of 10% w/w did not affect the cloud point of PP-15. DISCUSSION For treatment of acne and other conditions in which exfoliation of the cells at the skin
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