410 JOURNAL OF THE SOCIETY OF COSMETIC (:HEMISTS O. 4 LI,. 0.2 4 C, % w/v Figure 13. Effect of xanthan gum concentration on sedimentation volume of 5% heavy magnesium car- bonate suspensions. (O) no docusate sodium (I) 0.2% docusate sodium (') 0.25% docusate sodium (•') 0.3% docusate sodium. (Reproduced from reference 32 with permission of the copyright owner.) more xanthan gum was added, the suspensions became flocculated (based on micro- scopic observation) and were easily redispersible. Other experiments utilizing microscopy and sedimentation techniques demonstrated that suspension structure depended on whether salt or 'polymer served as the floccu- lating agent. Suspensions flocculated by salt were denser and more resistant to defloc- culation upon dilution with water. Synergism between salts and xanthan gum were noted. The addition of small quantities of sodium chloride, magnesium chloride, or calcium chloride made it possible for flocculation to occur at xanthan gum concentra- tions below those needed in the absence of salt. This was ascribed to a reduction in gum-particle repulsion which permitted adsorption of the gum to take place. CONCLUSIONS Physical stability of cosmetic suspensions requires consideration of a variety of factors. Quantitative measures of physical properties related to various aspects of stability help in optimizing product design. While surfactants are usually chosen because of their effects on wetting and polymers are selected on the basism-of their rheology, the possi- bility that these adjuvants may influence flocculation state should not be overlooked. A knowledge of the mechanisms involved in these processes is necessary in predicting how formulation components will influence suspension behavior. ACKNOWLEDGEMENTS I wish to express my thanks to the many students who worked with me in the labora- tory and contributed to the research described in this paper. I am also gratefhl to the Society of Cosmetic Chemists, the Kelco Division of Merck and Co., and Johnson and Johnson for financial support which made our work possible. REFERENCES (1) W. A. Zisman, "Relation of Equilibrium Contact AngLe to Liquid and Solid Constitution," in Co,- tact A,g/e, Wetti,g a,dAdhesio,, F. M. Fowkes, Ed. (American Chemical Society, 1964), pp 1-51. (2) S. W. Harder, D. A. Zuck, and J. A. Wood, Characterization of tablet surfaces by their critical surface-tension values. J. Pharm. Sd., 59, 1787- 1792 (1970).

SUSPENSION STABILITY 411 (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (]8) (19) (20) (21) (22) (23) (24) (25) (26) (27) (28) (29) (30) (31) (32) W.-C. Liao and J. L. Zatz, Surfactant solutions as test liquids for measurement of critical surface tension. J. Pharm. Sci., 68, 486-488 (1979). W.-C. Liao and J. L. Zatz, Critical surface tension of pharmaceutical solids. J. Pharm. Sci., 68, 488-494 (1979). C. F. Lerk, A. J. M. Schoonen, and J. T. Fell, Contact angles and wetting of pharmaceutical powders. J. Pharm. Sci., 65, 843-847 (1976). H. Schott and A. N. Martin, "Colloidal and Surface-Chemical Aspects of Dosage Forms," in American Pharmacy, 7th ed., L. W. Dirterr, Ed. (Lippincott, Philadelphia, 1974), pp 103-174. J. R. Van Wazer, J. W. Lyons, K. Y. Kim, and R. E. Colwell, Viscosity and Flow Measurement (Interscience, New York, 1963), pp 15-17. T. Gillespie, An extension of Goodeve's impulse theory of viscosity to pseudoplastic systems, J. Co//oidSci., 15, 219-231 (1960). S. E. Charm and W. McComis, Physical measurements of gums, Food Techno/., 948-953 (June 1965). R. S. Torrest, Rheological properties of aqueous solutions of the polymer Natrosol 250HHR, J. Rheo/., 26, 143-151 (1982). J. R. Van Wazer, J. W. Lyons, K. Y. Kim, and R. E. Colwell, Viscosity and Flow Measurement (Interscience, New York, 1963), pp 270-271. A. A. Daneshy, Numerical solution of sand transport in hydraulic fracturing, J. Petr. Techno/., 132-140 (January 1978). B. W. Barry, Dermato/ogica/Formulations (Dekker, New York, 1983), pp 303-304. R. J. Meyer and L. Cohen, The rheology of natural and synthetic hydrophilic polymer solutions as related to suspending ability, J. Soc. Cosmet. Chem., 10, 143-154 (1959). B. M. Berney and P. B. Deasy, Evaluation of Carbopol 934 as a suspending agent for sulphadimidine suspensions, Int. J. Pharm., 3, 73-80 (1979). J. L. Zatz and S. Knapp, Viscosity of xanthan gum solutions at low shear, J. Pharm. Sci., 73, 468-471 (1984). J. L. Zatz, Applications of gums in pharmaceutical and cosmetic suspensions, I&EC Prod. Res. Dev., 23, 12-16 (1984). P. A. Ciullo, Rheological properties of magnesium aluminum silicate/xanthan gum dispersions, J. Soc. Cosmet. Chem., 32, 275-285 (1981). B. A. Matthews and C. T. Rhodes, Use of the Derjaguin, Landau, Verwey and Overbeek theory to interpret pharmaceutical suspension stability, J. Pharm. Sci., 59, 521- 525 (1970). J. R. Feldkamp, D. N. Shah, S. L. Meyer, J. L. White, and S. L. Hem, Effect of adsorbed carbonate on surface charge characteristics and physical properties of aluminum hydroxide gel, J. Pharm. Sci., 70, 638-640 (1981). W.-C. Liao and J. L. Zatz, Effect of surfactant polyoxyethylene chain length on flocculation of local anesthetic suspension, J. Soc. Cosmet. Chem., 31, 107-121 (1980). W.-C. Liao and J. L. Zatz, Effect of added salts on flocculation of local anesthetic suspensions con- taining nonionic surfactants, J. Soc. Cosmet. Chem., 31, 123-131 (1980). J. L. Zatz, Effect of formulation additives on flocculation of dispersions stabilized by a nonionic surfactant, Int. J. Pharm., 4, 83-86 (1979). J. L. Zatz and R.-Y. Lue, Effect of polyols on physical stability of suspensions containing nonionic surfactant,J. Soc. Cosmet. Chem., 33, 149-155 (1982). T. W. Healy and V. K. LaMer, The adsorption-flocculation reactions of a polymer with an aqueous colloidal dispersion, J. Phys. Chem., 66, 1835-1838 (1962). W. Heller, Effects of macromolecular compounds in disperse systems, Pure App/. Chem., 12, 249-274 (1966). H. E. Ries, Jr. and B. L. Meyers, Flocculation mechanism: Charge neutralization and bridging, Science, 160, 1449-1450 (1968). J. P. Friend and J. A. Kitchener, Some physico-chemical aspects of the separation of finely-divided minerals by selected fiocculation, Chem. Eng. Sci., 28, 1071-1080 (1973). J. L. Zatz, L. Schnitzer, and P. Sarpotdar, Flocculation of sulfamerazine suspensions by a cationic polymer, J. Pharm. Sci., 68, 1491-1494 (1979). J. S. Tempio and J. L. Zatz, Flocculation effect of xanthan gum in pharmaceutical suspensions, J. Pharm. Sci., 69, 1209-1214 (1980). J. S. Tempio and J. L. Zatz, Interaction of xanthan gum with suspended solids, J. Pharm. Sci., 70, 554-558 (1981). J. L. Zatz, P. Sarpotdar, G. Gergich, and A. Wong, Effect of surfactants on the flocculation of magnesium carbonate suspensions by xanthan gum, Int. J. Pharm., 9, 315-319 (1981).