SUSPENSION STABILITY 407 0.4 0.2 --3 --1 1 LOG C Figure 10. Sedimentation volume of sulfamerazine suspensions containing dioctyl sodium sulfosuccinate in the presence of various Primafloc C-3 concentrations. Key: curve 1, 0.2% dioctyl sodium sulfosuccinate curve 2, 1.0% dioctyl sodium sulfosuccinate. (Reproduced from reference 29 with permission of the copy- right owner, the American Pharmaceutical Association.) A third flocculation mechanism is based on the bridging of particles by polymers. This involves having a single polymer molecule adsorb onto the surface of two or more particles (25-28). Intuitively, highly asymmetric polymer molecules of high molecular weight are needed to perform in this way. Flocculation of negatively charged sulfamerazine particles by a cationic polymer has been described (29). Low polymer concentrations had little effect on sedimentation volume but, at a critical value, a precipitous rise in sedimentation volume took place, showing that the suspension had become flocculated (Figure 10). At still higher poly- mer concentrations, sedimentation volume once again decreased the suspension was now deflocculated once more. Measurements of redispersibility paralleled the sedimen- tation volume data: suspensions with low sedimentation volume (deflocculated) were caked while those with higher sedimentation volume (flocculated) were easily redis- persed. These results were explained using the models depicted in Figure 11 (29). With either c Figure 11. Suggested mechanism for the behavior of Primafioc C-3 in suspensions. Key: a, low polymer concentration, defiocculated suspension b, fiocculation by bridging c, defiocculation at high polymer concentrations. (Reproduced f?om reference 29 with permission of the copyright owner, the American Pharmaceutical Association.)

408 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table III Degree of Flocculation of Suspensions in Water Containing 5 g of Solid/100 ml Medium Degree of Flocculation Aluminum Hydroxide Magnesium Carbonate Xanthan Gum (Conc., % w/v) No Salt 0.9% NaCI No Salt 0.9% NaC1 0 3.6 4.6 1.4 1.4 0.03 5.7 4.8 2.0 1.7 0.10 6.4 5.6 2.1 1.9 0.15 6.4 6.5 2.1 - 0.20 6.8 6.3 2.2 2.7 small concentrations or no polymer present, the particles were kept separate by their negative charge (Figure 1 la). Flocculation at intermediate polymer concentrations was due to bridging (Figure l lb). At much higher polymer concentrations, adsorption caused the surface of the particles to become positively charged, once again resulting in defiocculation (Figure 1 lc). The effect of xanthan gum, an anionic polymer, on flocculation of suspended solids was investigated by microscopy, sedimentation, and particle size measurements. The degree of flocculation was calculated by dividing the sedimentation volume for the suspension under consideration by that of a completely deflocculated suspension of the same mate- rial at the same concentration. Some values are reproduced in Table lit (30). As is evident from Table ttt, xanthan gum increased the extent of flocculation in sus- pensions of aluminum hydroxide and magnesium carbonate whether salt was added to the suspension or not. The extent of flocculation of calcium carbonate suspensions was increased slightly by xanthan gum, while zinc oxide suspensions experienced a decrease in the degree of flocculation. The flocculation mechanism in these suspensions was investigated by studies of adsorp- tion an d zeta potential (31). Values of saturation adsorption, obtained by fitting the Langmtiir isotherm to the adsorption data are collected in Table IV. A number of factors combine to influence the adsorption of polymers at the solid-liquid interface. These include polymer shape, the amount of surface area available, solid-polymer at- traction, and repulsion of neighboring adsorbed molecules when the polymer is charged. A reduction in polymer-polymer charge repulsion accounted for the higher adsorption observed in suspensions containing added sodium chloride (Table IV). Table IV Adsorption of Xanthan Gum by Pharmaceutical Solids Substance Saturation Adsorption, mg/g Water 0.9% NaC1 Solution Magnesium carbonate Aluminum hydroxide Calcium carbonate Zinc oxide 6.67 16.6 3.59 4.55 9.83 22.6 11.1 7.30