150 JOURNAL OF COSMETIC SCIENCE RESULTS FILM CHARACTERIZATION AND STABILITY In vitro dissolution of the film in water. The time needed to fully dissolve the film ranged from 10 seconds to 15 seconds. In comparison, under the same experimental setting, the dissolution of a commercial pullulan-based breath-freshening strip (Cool Mint Listerine PocketPaks™, Warner-Lambert Consumer Healthcare) took between 35 and 40 sec­ onds. Water content and uptake. As the films are intended to quickly dissolve in water, their sensitivity to moisture and water uptake needs to be carefully assessed. Figure 2 shows the moisture sorption/desorption kinetics of the films at 25°C. As relative humidity (RH) increases, the uptake of moisture increases the film weight. At 80% RH, a weight increase of approximately 50% was measured. However, no hysteresis was observed, i.e., the film weight decreased according to the same kinetics when the RH was brought down. This result indicates that moisture uptake at high RH does not induce any structural modification of the film or lead to any significant chemical degradation. Table I shows the weight, water content, and act1v1ty variations after one month of storage at 45°C. At initial time, the water content and activity of the films were both very low, showing that the drying conditions used during the manufacturing process was efficient. After one month at 45 °C, a slight, although non-significant, variation in weight was observed, while the overall water content and activity remained at initial values. Adenosine content over time. As shown in Table I, the adenosine content per film after one month at 45°C was equal to 96% of the value at initial time. Date: 16 Dec 2005 Time: 5:13 pm File: Loreal 5000165 - Fri 16 Dec 2005 17-13-51.xls Sample: Loreal 5000165 50 45 40 C:- 35 0 ,.:._ 30 � :lJ 25 � 20 � 15 .r. 0 10 5 -6 DVS-Th&So,pliof,Solution DVS Isotherm Plot Sample% P/Po Temp: 25.1 ·c Meth: Loreal full cyde.sao M(0): 10.3996 80 90 @ Surface Measmement Systems Ltd UK 1996-2006 Figure 2. Moisture sorption/desorption kinetics of the dissolvable film from 0% RH to 80% RH.

Initial time (TO) After 1 month's storage at 45°C DISSOLVABLE ANTI-WRINKLE FILM Table I Stability of the Dissolvable Adenosine-Containing Film Over Time Film weight (mg) (n = 20) 10.6 ± 0.5 11.3 ± 0.8 Water content (% w/w) (n = 15) 10% 10% Water activity (n = 3) 0.35 VISUALIZATION OF FILM DEPOSITION ON THE SKIN 151 Adenosine content (mg/film) (n = 5) 0.104 ± 0.001 0.100 ± 0.001 Scanning electron microscopy (SEM) showed that one hour after dissolution with water on the skin, the film formed a continuous and homogeneous layer fully covering the wrinkle area onto which it was applied (Figure 3B). After six hours, the film dried and the layer became partially discontinued as some solid pieces of the film detached. However, large skin surfaces were still covered with the film layer six hours after application (Figure 3C). EVALUATION OF ANTI-WRINKLE EFFICACY IN FEMALE VOLUNTEERS As measured by FOITS, both the Ra and Rz skin roughness parameters decreased following the application of the 1 % adenosine-containing film. The reduction in rough­ ness was evidenced as early as three weeks after starting product application and reached a level of -4.5% and -5.3% for Rz and Ra, respectively (Table II). At three weeks, the reduction of the skin roughness parameters obtained with the dissolvable film was significantly higher than that induced by the placebo cream. An improvement in the facial relief in the periorbital region was still observed at eight weeks (Table II). DISCUSSION The present study investigated the formulation and the efficacy of a thin, water-soluble film to deliver a cosmetic active ingredient, adenosine, onto the skin. Preformulation data showed that low-molecular-weight cellulose derivatives, e.g., hydroxypropylcellu­ lose or hydroxypropylmethylcellulose were suitable polymers to formulate such films. Indeed, other polymers widely used to formulate oral strips, such as pullulan, are less suitable for skin application. For example, upon drying, pullulan becomes very sticky, leading to unpleasant cosmetic effects (data not shown). The film we developed quickly dissolves in water and can be spread on the skin within seconds when applied with a drop of water. It also adsorbs moisture to a large extent when exposed to high RH. Water uptake of cellulose-based films was found to increase sharply in a high-water-activity environment (6). It is also hypothesized that the high level of glycerin present in the formulation (30%) strongly increases the water uptake of the film. It was previously reported that adding 30% glycerin in hydroxypropylcellulose films dramatically increases water permeability and film elongation (7). Howf'vf'r, in a suitable packaging, the film appears stable over time and no degradation of the active ingredient adenosine is detected. The film is a substantially dry dosage form and hence