a. CJ � U) 0 CJ U) 60000 40000 20000 0 COSMETIC FORMULATIONS WITH ARGIRELINE® 165 -25 ° C24h -25 ° C 7 days --IE-25 ° C 30 days 0.5 2.5 10 100 Speed (rpm) Figure 3. Viscosity vs speed of Argireline® gel maintained at 25 ° C as a function of storage time. influence of the membrane on the results. For this study, a 5 mg ml- 1 solution of Argireline® was used as the donor phase, and PBS (pH 5.6) was used as the solvent to prepare the drug in the donor phase. This buffer was also used as the receptor phase. We previously verified that sink conditions were maintained. Diffusion was slightly more rapid with the nylon membrane, and we therefore used this membrane for subsequent studies. Both preparations were subjected to in vitro diffusion assays in a Franz cell. All assays were performed under the same conditions as described above in the section on membrane selection. Release assays to measure the amount and percentage of active principle in the receptor cell (Figures 9 and 10) showed that release was greater from the cream formulation (50% after five hours) than from the gel (20% after five hours). The difference may reflect thermal gelling of the latter formulation upon contact with tht clisptrsion meclium in vitro1 an effect that would be expected to increase viscosity. Diffusion of the peptide was first detected ten minutes after the essay was started.

166 JOURNAL OF COSMETIC SCIENCE 60000 -,------------------- - 4 ° C24h -+- 4 ° C 7 days - 4 ° C30days 40000 20000 0 +--+--+---+---+----+---+--..==•=::111 0.5 2.5 10 100 Speed (rpm) Figure 4. Viscosity vs speed of Argireline® gel maintained at 4°C as a function of storage time. Table V Chromatographic Parameters of Stability at Different Temperatures Temperature (°C) 25 40 60 RT 18.5 18.5 18.5 AUC 1899098 1119000 781954 µm/ml 500 294 205 % 100 58.80 41 Although the rate of absorption below 50% with both formulations may appear low, the results in general show that both the cream and the gel formulations satisfied the requirements for cosmetic products intended for topical application, since the cosmeti­ cally active substance, 8-acetyl hexapeptide, is targeted to treat the most superficial layers of the skin (23).