396 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 0.030 0.025 0.020 I I I I 14 16 18 20 •L/2• Figure 2. Penetration of aspirin granules by nonionic surfactant solutions. Vertical bars indicate standard deviation. (Reproduced from reference 4 with permission of the copyright owner, the American Pharma- ceutical Association.) Figure 3 contains Zisman plots for aspirin, based on contact angles determined in different ways (4). The solid circles are data from penetration measurements. The other data are from direct measurement of contact angles on aspirin tablets. Allowing the drop to remain in contact with the aspirin surface results in a lowering of the contact 1.00 -- 0.95 0.90 0.85 0.80 30 35 40 45 SURFACE TENSION, dynes/era Figure 3. Cosine of contact angle on aspirin as a function of liquid surface tension. (/•) dynamic angle (O) static angle ([•) angle after 5 min. (O) angle from penetration study. (Reproduced from reference 4 with permission of the copyright owner, the American Pharmaceutical Association.)

SUSPENSION STABILITY 397 angle, although extrapolation to cos 0 = 1 always resulted in the same value for the critical surface tension. The points from the penetration measurement were closest to those for the angle measured while the drop was growing on the tablet surface, the so-called advancing contact angle. The same pattern was observed in studies on phena- cetin and several sulfa drugs, but not salicylic acid, for which the contact angles mea- sured by direct observation were much too low. This may have been due to the very rough surface generated by compaction (4). Critical surface tension values for other powdered solids have been published (5,6). Critical surface tension values for several powdered substances are collected in Table I. Many of the organic drug compounds studied to date have values in the neighborhood of 30-32 dyn/cm. The value for magnesium stearate, 22 dyn/cm, is typical of surfaces made up of long hydrocarbon chains oriented normal to the plane of the surface. Knowing the value of the critical surface tension helps in deciding whether a wetting agent is necessary as well as in choosing a suitable agent. For example, if a sulfur suspension in water has to be prepared, it is apparent that a wetting agent is needed since the surface tension of water (about 72 dyn/cm) is so much greater than the critical surface tension of sulfur (30 dyn/cm from Table I). Use of a surfactant that lowers the water surface tension to 30 dyn/cm or less will cause spontaneous wetting to take place. If the surface tension of an aqueous solution of the wetting agent is somewhat higher than 30 dyn/cm, wetting is still possible with the aid of agitation. DISPERSION Wetting is only one aspect of complete dispersion. Mechanical energy may be needed to separate the primary particles composing the agglomerates. Whether these particles will then recombine depends on the balance of attractive and repulsive forces between particles. So-called dispersing agents are usually charged molecules that adsorb onto solid surfaces and increase repulsion between particles. Suspensions in which primary particles remain separate are referred to as defiocculated. Flocculation, the process de- scribing agglomeration of primary particles by weak bonding forces, is often used delib- erately in suspensions in which sedimentation cannot be avoided. More will be said about this when we discuss stabilization of suspensions against caking. SEDIMENTATION Except for very dilute colloidal dispersions, in which Brownian motion counteracts gravity, suspensions undergo sedimentation as a result of unequal gravitational pull on Table I Critical Surface Tension Values for Some Powders Critical Surface Tension Substance (dyn/cm) Reference Sulfadiazine 33 4 Aspirin 32 4 Salicylic Acid 31 4 Sulfur 30 6 Magnesium Stearate 22 2