J. Cosmet. Sci., 66, 95–111 (March/April 2015) 95 Optimal aluminum/zirconium: Protein interactions for predicting antiperspirant effi cacy using zeta potential measurements SHAOTANG YUAN, JOHN VAUGHN, IRAKLIS PAPPAS, MICHAEL FITZGER ALD, JAMES G. MASTERS, and LONG PAN, Colgate-Palmolive Company Piscataway, NJ 08854 Accepted for publication February 11, 2015 Synopsis The interactions between commercial antiperspirant (AP) salts [aluminum chlorohydrate (ACH), acti- vated ACH, aluminum sesquichlorohydrate (ASCH), zirconium aluminum glycine (ZAG), activated ZAG], pure aluminum polyoxocations (Al13-mer, 30 Al -mer), and the zirconium(IV)–glycine complex ¯12+ ¡ ° 6 2 4 4 8 8 Zr O OH H O Gly (CP-2 or ZG) with Bovine serum albumin (BSA) were studied using zeta potential and turbidity measurements. The maximal turbidity, which revealed the optimal interac- tions between protein and metal salts, for all protein–metal salt samples was observed at the isoelectric point (IEP), where the zeta potential of the solution was zero. Effi cacy of AP salts was determined via three parameters: the amount of salt required to fl occulate BSA to reach IEP, the turbidity of solution at the IEP, and the pH range over which the turbidity of the solution remains suffi ciently high. By comparing active salt performance from this work to traditional prescreening methods, this methodology was able to provide a consistent effi cacy assessment for metal actives in APs or in water treatment. INTRODUCTION Charge neutralization (coagulation) and sweep fl occulation are well-known mechanisms of action between cationic coagulants and organic matter in the treatment of waste water (1,2). Salts of aluminum such as aluminum polyoxocations, aluminum chlorohydrate (ACH), or aluminum chloride (AlCl3) are often selected to treat waste water because they exhibit strong coagulation and fl occulation behavior (3–6). Besides water treatment and many other applications, these salts are the predominant active ingredients employed in antiperspirant (AP) formulations, which reduce more than 20% perspiration and show considerable odor inhibition in the underarm area (7,8). “Plug Theory,” a well-known theory of sweat reduction proposed by Reller and Luedders (9), postulates that dissolved AP salts diffuse into the sweat duct and are hydrolyzed upon contacting with sweat to form an amorphous metal hydroxide plug that physically blocks the escape of sweat from Address all correspondence to Long Pan at long_pan@colpal.com.

JOURNAL OF COSMETIC SCIENCE 96 the duct. On the basis of the plug model, it is clear that the effi cacy of AP salts critically dependents on the speed and depth with which the salt penetrates into the sweat glands to form a strong plug—deeper and less superfi cial plugs will be more substantive (10– 14). Bearing this in mind, actives of a smaller particle size should show better effi cacy. Consequently, the assessment of AP effi cacy lies mostly in particle size analysis, i.e., size- exclusion chromatography and light scattering. In addition to Plug Theory, other interpretations of this process are also plausible. For instance, previous research has investigated the interaction and formation of fl oc between metal cations or complexes and biomolecules (15–21). Since biomolecules (e.g., proteins) are important components of sweat (22), it is also conceivable that metal ions of AP salts react with the biomolecules in sweat to form water-insoluble complexes, which in turn triggers plug formation in the sweat gland. This mechanism would be similar to the mechanism of coagulation and fl occulation in water treatment. These interactions be- tween metal cationic species and biomolecules can be analyzed by zeta potential (ζ-potential) characterization, which is a powerful technique in the evaluation of coagu- lant agents in water treatment (13,23–26). ζ-Potential is the surface charge of a particle in a colloid system, and is a strong indica- tor for fl oc formation (23–28). Isoelectric point (IEP) or point of zero charge is the pH at which the solution has a zero ζ-potential. At this point, the lack of repulsive forces between dissolved substances and suspended colloids induces coagulation and precipi- tation (24). Gauckler and coworkers (27) proposed a two-step adsorption of bovine serum albumin (BSA) onto Al2O3 particles surface by ζ-potential measurement. Another study by Perry and coworkers (16) also used ζ-potential to demonstrate the interaction of aluminum polyoxocations (Al13-mer and Al30-mer) with BSA or lyso- zyme. However, to date, the critical coagulation ratios between commercial APs and a representative protein (BSA) have not been systematically characterized by using ζ-potential measurement. In this report, we present what’s believed to be the fi rst study of commercial AP actives and BSA by using ζ-potential and turbidity measurements with a focus on the forma- tion of insoluble AP–BSA complexes at the pH where ζ-potential of the solution is zero, and we use the term IEP to indicate this pH of AP–BSA complex under our experiment condition. We envision a critical ratio of polycation/protein characterized by the point where the ζ-potential of the system is zero. This ratio governs the precipitation process due to the optimal interaction between protein and AP salts, and would serve as an indicator of the effi cacy of the species in question. The goal of this work is to explore the possibility of using ζ-potential as a means to predict the effi cacy of AP actives and other simple Al or Zr salts and to guide us to develop more effi cacious AP salts. We also note that the proposed mechanism of plug formation with proteins in the sweat duct is very similar to the accepted mechanism of coagulation and fl occulation in primary water treatment. MATERIALS AND METHODS BSA and glycine were purchased from Sigma-Aldrich (St. Louis, MO). ACH, [Al2(OH)5Cl·H2O, 81.6% actives, 25.2% Al] and activated ACH, [Al2(OH)5Cl·H2O, 82% actives, 25.4% Al] aluminum sesquichlorohydrate (ASCH), [Al2(OH)4.8Cl1.2·H2O,