TITRATION OF ANTIPERSPIRANT ACTIVES 117 ity did not increase until 1.4 ml ooe 0.5 N NaOH was added. However, the pH increased from the beginning ooe the titration. The turbidity reached a maximum when approxi- mately 5.0 ml ooe 0.5 N NaOH was added. The pH was 11.3 at this point. Continued addition ooe base led to the partial dissolution ooe the precipitate. No attempt was made to identify the precipitate, but it had different properties From the precipitates produced by aluminum chloride or ACH, as these precipitates were completely soluble at high pH. We propose that the precipitate produced by AZG- is a mixture ooe aluminum hydroxide and zirconium hydroxide. Aluminum hydroxide is soluble in both acid and base while zirconium hydroxide is soluble only in acid (16). Thus, the decrease in turbidity at high pH may be due to the dissolution ooe the aluminum hydroxide phase but not the zirconium hydroxide phase. Research is needed to characterize the precipitate produced From AZG-. Although ACH and AZG- are the most widely used antiperspirants, advances in their preparation have led to activated ACH (10) and activated AZG- (11). AZG-' is generally recognized as the most effective antiperspirant active currently in wide use (10,11). The potentiometric/turbidometric titrations ooe aluminum chloride, ACH, ACH ', AZG-, and AZG -• were determined in order to compare their abilities to oeorm precipitates. For clarity, only turbidometric titrigraphs are shown in Figure 5. The aluminum chloride turbidometric titrigraph suggests a lower plug-forming capability and possibly a lower antiperspirant efficacy. This conclusion is not consistent with reports that aluminum chloride inhibits sweating by 60% to 70% and that ACH- or AZG--containing products inhibit sweating by 30% to 55% (2,17). It was hypothesized that lower-molecular- weight species, such as aluminum chloride, can diffuse more deeply into the sweat ducts because ooe their small size (2). In addition, it was proposed that precipitation from aluminum chloride, in a sweat duct with limited buffer capacity, would occur at a slower rate and produce an occlusive plug in the sweat duct at a greater depth because ooe the higher neutralization requirement (2). Other researchers have suggested that aluminum 1 • ACH .8 .6 .4 .2 0 AICI 3 0 5 10 15 20 25 Volume of 0.5 M NaOH (ml) Figure 5. Turbidometric titrigraphs of 0.1 M A1C13, 0.1 M ACH, 0.1 M ACH', 0.1 M AZG, and 0.1 M AZG' titrated against 0.5 N NaOH. The dashed curves represent ACH' and AZG'.

118 JOURNAL OF COSMETIC SCIENCE chloride achieves its antiperspirant effectiveness by destruction of the integrity of the acrosyringium or by a non-specific anti-inflammatory effect (2,18). The difference between the precipitates formed from ACH and ACH' is seen in the greater volume of base required to completely dissolve the precipitate formed from ACH'. A similar trend is evident in the comparison of AZG' and AZG. Furthermore, on a molar basis, AZG' produced the largest turbidity value of any of the antiperspirant actives tested. This property may be partly responsible for the high degree of efficacy attributed to AZG' (10,11). The experimental approach used in this study provides new insight into the precipita- tion behavior of antiperspirant actives. The potentiometric/turbidometric titration tech- nique may prove useful in establishing specifications for antiperspirant actives. REFERENCES (1) A. H. Rosenberg and J. J. Fitzgerald, "Chemistry of Aluminum-Zirconium-Glycine (AZG)Complexes," in Antiperspirants and Deodorants, 2nd ed., K. Laden, Ed. (Marcel Dekker, New York, 1999), p. 138. (2) H. H. Relier and W. L. Leudders, "Pharmacologic and Toxicologic Effects of Topically Applied Agents on the Eccrine Sweat Glands," in Advances in Modern Toxicology, Vol. 4, F. N. Marzulli and H. I. Maibach, Eds. (Wiley, New York, 1977), pp. 1-54. (3) R. P. Quatrale, A. H. Waldman, J. G. Rogers, and C. B. Felger, The mechanism of antiperspirant action by aluminum salts. I. The effect of cellophane tape stripping on aluminum salt-inhibited eccrine sweat glands,J. Soc. Cosmet. Chem., 32, 67-73 (1981). (4) R. P. Quatrale, D. W. Coble, K. L. Stoner, and C. B. Felger, The mechanism of antiperspirant action by aluminum salts. II. Histological observations of human eccrine sweat glands inhibited by alumi- num chlorohydrate, J. Soc. Cosmet. Chem., 32, 107-136 (1981). (5) R. P. Quatrale, D. W. Coble, K. L. Stoner, and C. B. Felger, The mechanism of antiperspirant action of aluminum salts. III. Histological observations of human eccrine sweat glands inhibited by alumi- num zirconium chlorohydrate glycine complex, J. Soc. Cosmet. Chem., 32, 195-221 (1981). (6) R. P. Quatrale, E. L. Thomas, and J. E. Birnbaum, The site ofantiperspirant action by aluminum salts in the eccrine sweat glands of the axilla, J. Soc. Cosmet. Chem., 36, 435-440 (1985). (7) S.A. McWilliams, I. Montgomery, D. McE. Jenkinson, H.Y. Elder, S. M. Wilson, and A.M. Sutton, Effects of topically-applied antiperspirant on sweat gland function, Br. J. Dermatol., 117, 617-626 (1987). (8) D. L. Teagarden, J. L. White, and S. L. Hem, Aluminum chlorohydrate III: Conversion to aluminum hydroxide, J. Pharm. Sci., 70, 808-810 (1981). (9) The United State Pharmacopoeia (United States Pharmacopeial Convention, Rockville, MD, 2000), pp. 83-87, 89-91, 92-103. (10) J.J. Fitzgerald and A. H. Rosenberg, "Chemistry of Aluminum Chlorohydrate and Activated Alumi- num Chlorohydrates," in Antiperspirants and Deodorants, 2nd ed., K. Laden, Ed. (Marcel Dekker, New York, 1999), pp. 83-136. (11) A.H. Rosenberg and J.J. Fitzgerald, "Chemistry of Aluminum-Zirconium-Glycine (AZG) Com- plexes," in Antiper•J)irants and Deodorants, 2nd ed., K. Laden, Ed. (Marcel Dekker, New York, 1999), pp. 137-168. (12) M. K. Wang, J. L. White, and S. L. Hem, Influence of acetate, oxalate, and citrate anions on precipi- tation of aluminum hydroxide, Clays Clay Miner, 31, 65-68 (1983). (13) C.J. Serna, J. L. White, and S. L. Hem, Factors affecting homogeneous precipitation of aluminum hydroxide gel, J. Pharm. Sci., 67, 1179-1181 (1978). (14) J. D. Hem and C.E. Roberson, Form and stability of aluminum hydroxide complexes in dilute solution. Geological S•rvey Water-Supply Paper 1827-A, A47 (1967). (15) K. Laden, "Antiperspirants and Deodorants: History of Major HBA Market," in Antiperspirants and Deodorants, 2nd ed., K. Laden, Ed. (Marcel Dekker, New York, 1999), pp. 3-6. (16) The Merck Index (Merck Research Laboratories, Whitehouse Station, NJ, 1996), pp. 61, 1738. (17) K. Laden, "Antiperspirants and Deodorants: History of Major HBA Market", in Antiperspirants and Deodorants, 2nd ed., K. Laden, Ed. (Marcel Dekker, New York, 1999), p. 2. (18) E. L. Opie, On the relation of necrosis and inflammation to denaturation of proteins,J. Exp. Med., 115, 597-608 (1962).