216 JOURNAL OF COSMETIC SCIENCE Table III Mean Diameters of Swollen Micelies Mean diameters (nm) Miceliar solution 24 h after preparation Mean diameters (nm) after 3-month stability tests A 11.2 (0.7)* 5% 2.4 (0.8) 4% 41.0 (13.5) 95% 63.7 (31.9) 96% B 41.0 (15.0) 100% 51.8 (5.1) 100% C 5.6 (0.8) 2% 3.2 (0.5) 4% 88.4 (23) 98% 83.4 (31.4) 96% D 7.7 (3.3) 6% 11.2 (3.0) 13% 96.0 (39) 94% 98.3 (39.1) 87% E 20.5 (7.7) 10% 8.5 (2.9) 11% 84.6 (26.0) 90% 55.7 (8.2) 99% F 16.0 (6.8) 10% 80.0 (20.1) 28% 150.0 (60.1) 90% 657.6 (200.6) 72% G 12.5 (4.0) 6% 19.8 (6.0) 4% 183.0 (30.3) 94% 155.4 (42.2) 96% H 8.4 (3.0) 7% 5.6 (O.8) 4% 145.0 (46.0) 93% 129.9 (45.1) 96% I 15.4 (6.1) 10% 9.7 (1.0) 10% 204.0 (90.3) 90% 119.0 (40.6) 90% L 49.1 (14.3) 25% 54.1 (24.3) 27% 377.0 (10.8) 75% 399.0 (140.5) 93% * Standard deviations are given in parentheses. 4.0% w/w citral = 1.0% w/w surfactant mixture 2 = 16.0% w/w hexylene glycol = 1.85% w/w ethanol -- 2.27% w/w water -- 74.88% w/w. For miceliar solution O: linalool = 4.0% w/w citral = 1.0% w/w surfactant mixture 3 = 14.4% w/w hexylene glycol = 1.85% w/w ethanol = 2.27% w/w water = 76.48% w/w. The pH values of all the miceliar solutions were in the 4.5-5.0 range. The maximum achievable citral concentration was 0.5% w/w in those micellar solutions containing surfactant mixture 1, while surfactant mixtures 2 and 3 allowed up to 1.0% w/w citral to be solubilized higher percentages of citral could be solubilized using higher percentages of surfactant, cosurfactant, and ethanol. Since the aim of this study was to use as little solubilizer and surface agent as possible, we decided not to increase the amount of citral, as the fragrance of the blend of the odorous molecules was quite pleasant. Indeed, the amount of hexylene glycol was lower than the amount of propylene glycol used previously (5) to solubilize some odorous molecules in the presence of different surfactants moreover, the potential irritant action of hexylene glycol is much lower than that of propylene glycol. The surfactant mixtures used consisted of non- ethoxylated molecules derived from natural molecules such as glucose and fatty acids, and of lecithin, all of which are mild and skin-compatible substances. Microemulsions that were formulated for potential use as bath oils could only be ob- tained with some of the lipids employed as oil phase. Their compositions are reported in Table IV. Using surfactant mixture 1, it was possible to obtain a single microemulsion with n-dodecanol as oil, while with surfactant mixture 3, no microemulsion was obtained.

DISPERSE SYSTEMS AS TOPICAL VEHICLES 217 Table IV Compositions of Microemulsions of Linaloo! (w/w percentages) No. Linalool s.m. 1 s.m. 2 n-Dodecanol IPP C•2_•5 AB Water Hexylene glycol EtOH 1 5.0 -- 25.5 5.0 -- -- 60.38 1.85 2.27 2 5.0 -- 20.0 -- 5.0 -- 65.88 1.85 2.27 3 5.0 -- 18.0 -- -- 5.0 67.88 1.85 2.27 4 5.0 24.0 -- 5.0 -- -- 61.88 1.85 2.27 Table V Mean Diameters of Microemulsions Miroemulsion Mean diameters (nm) 24 h after preparation Mean diameters (nm) after 3-month stability tests 1 5.6 (0.8)* 6% 4.2 (1) 5% 72.2 (25) 94% 74.8 (30) 95% 2 14.5 (5) 5% 7.9 (5) 4% 212.0 (36) 95% 230.6 (70) 96% 3 21.4 (8) 5% 16.8 (8) 5% 252.3 (48) 95% 260 (80) 95% 4 3.2 (0.3) 8% 4.6 (1) 7% 55.0 (8) 92% 55.2 (15) 93% *Standard deviations are given in parentheses. Surfactant mixture 2 produced microemulsions using n-dodecanol, IPP, or C12_15 AB as oils. Neither caprylic-capric triglyceride (due to its high steric impediment), nor cyclo- methiocone (well known to be incompatible with most lipids), nor mineral oil (probably as a consequence of its low polarity) gave rise to microemulsified systems in the experi- mental conditions. The mean diameters of the microemulsion droplets did not vary significantly after three-month freeze-thaw and centrifuging tests, as described in the Experimental section (Table V). The systems with IPP and C•2_•5AB were not completely transparent they had a slight opalescence that would probably convert them in miniemulsions, particu- larly emulsified systems with mean droplet diameters in the 100-400 nm range (12). After assessing the physical stability of the miceliar solutions over time, it was important to evaluate the stability of both odorous molecules towards oxidation following oxygen uptake. Indeed, autooxidation of citral, involving its aldehydic group, takes place in aqueous solutions in acidic conditions. The highest degradation rate is noted at pH lower than 3.0, but already at pH 6.5 some instability can be noted. At low pH values the concentration of citral decreases rapidly by a series of cyclization and oxidation reactions that have been studied in detail, even if unequivocal evidence to confirm the deterio- ration mechanism still appear to be lacking. In the literature (13), a possible deterio- ration mechanism is reported as in Scheme 2. Linalool possesses an allylic proton at C 5 that is relatively unhindered and thus acces- sible for oxidation. The resultant free radical (after isomerization) is tertiary allylic in nature it is therefore very stable and has the potential to terminate oxidative chain reactions (14) (See Scheme 3).