DIFFUSION OF PRESERVATIVES 245 140 12o 80 6o 40 20 0 A 2 4 6 8 diffusion time (hours) , 70 • 60 ß • 40 •3o 0c 0 B 2 4 6 8 diffusion time (hours) 70 "$ 60 • 50 '• 40 • 30 • 20 .• 1o c 2 4 6 8 10 diffusion time (hours) 70 •50 -=• 40 • 3o $2o o 10 0• 0 D 2 4 6 8 diffusion time (hours) , i 0 2 4 6 8 10 diffusion time (hours) Figure 2. "In vitro" diffusion kinetics of methyl- (O), ethyl- ([•) and propyl- (O)-parabens incorporated in the reported topical dosage forms. A bimembrane system was employed: a silicone-based membrane (250- pm thickness) in contact with the donor phase, and a nylon-based membrane (150-pm thickness), 0.22-pm pore size) in contact with the receptor phase. The results reported represent the mean values + SD of six independent experiments. A: Aqueous solution. B: Water-in-oil emulsion. C: Oil-in-water emulsion. D: Pemulen gel. E: Carbopol gel. calculated diffusion coefficients for parabens incorporated into the different topical forms are reported in Table III. Figure 3 shows a comparison between the diffusion coefficients of the different parabens from topical formulations.

246 JOURNAL OF COSMETIC SCIENCE Table III "In vitro" Diffusion Coefficients of Preservatives Incorporated in Different Topical Forms Determined Utilizing Franz-Type Diffusion Cell Preservative Jo ' lag/cm2h C (mg/ml) Jn ' cm/h x 10 3 log Jn Aqueous solution Methylparaben 17.48 0.5 34.96 1.54 Ethylparaben 14.39 0.5 28.77 1.45 Propylparaben 11.55 0.5 23.16 1.36 W/O emulsion Methylparaben 3.48 0.5 6.96 0.84 Ethylparaben 3.37 0.5 6.74 0.82 Propylparaben 1.08 0.5 2.16 0.33 O/W emulsion Methylparaben 4.87 0.5 9.74 0.98 Ethylparaben 1.40 0.5 2.80 0.44 Propylparaben 0.37 0.5 0.74 -0.13 Pemulen gel Methylparaben 0.67 0.5 1.34 0.12 Ethylparaben 1.27 0.5 2.54 0.40 Propylparaben 1.34 0.5 2.67 0.42 Carbopol gel Methylparaben 3.95 0.5 7.90 0.89 E thylparaben 8.47 0.5 16.94 1.22 Propylparaben 9.22 0.5 18.44 1.26 The reported results represent the average of six independent experiments. In the case of aqueous solutions, the diffusion coefficients of parabens (Jn values) are at least fivefold higher than in the case of viscous forms. In addition, the diffusion coef- ficients are a function of the substituent of preservatives: the higher the solubility, the higher the diffusion of parabens. The same behavior is reliable for the emulsions, in particular in the case of the O/W, where the normalized fluxes (J,) were 9.74, 2.8, 0.74 cm/h x 103 for MP, EP, and PP, respectively. On the contrary, in the case of the hydrophilic gels, the higher the parabens solubility, the lower the diffusion coefficients. In particular, in the case of Carbopol gel, J, values were 7.9, 16.94, and 18.44 cm/h x 103 for MP, EP, and PP, respectively. The different types of vehicles could account for the differences in the diffusion coeffi- cients of the preservatives. MP and EP exhibit more affinity with the hydrophilic matrix of gels in comparison to PP, which, being more insoluble, is less retained, resulting in a higher diffusion coefficient. Moreover, in the case of Pemulen gel, Jn values are lower with respect to those exhibited by parabens incorporated in Carbopol gel. The trend can be attributed to the different lipophilicity of the resins in fact, the acrylates/C10-30 alkyl acrylate crosspolymer, having C10-C30 chains, is able to dissolve parabens better than the carboxy vinyl polymer carbomer. This behavior is particularly evident for PP, which is much more retained by Pemulen gel in comparison to Carbopol gel (J, of 2.67 versus 18.44 cm/h x 103) due to the chemical affinity of PP to the acrylates/C10-30