FACTORS INFLUENCING THE SELECTION OF SUSPENDING AGENTS By CLIFFORD W, CHONG* Presented September 20, 1962, Seminar, New York City W•E• •)EV•LOP•SO a suspension form of a drug, the formulator is faced with a number of problems. One of these is choosing the right suspension vehicle for his formula. In many cases, the choice of the vehicle is governed by what has been used in previous suspension products or by what has been described in the literature as having been tried and found useful, however usually in specific applications. This practice of following the dictates of convention does provide a starting point, but it has often led to the failure of many suspension systems. The reason for this is the complex nature of suspension systems. Higuchi (1), in his discus- sion of the physico-chemical aspects of suspension formulation, points out the difficulties one might expect when relating experimental data with suspension performance. The formulatot encounters a great number of variables when working with suspensions. There are, for instance, the physical properties of the particle, such as the size, shape and density, the density of the vehicle, the volume ratio of the two phases, the extent of particle flocculation, the flow characteristics of the suspension and, probably more important, the flow characteristics of the suspension vehicle. In addition, the variables which influence the chemical stability of the suspension must be considered. Because of these many variables, it seems unlikely that a vehicle used satis- factorily in one suspension formula could be equally as effective in another, unless the physical and chemical properties of both happened to be the same. For this reason, each suspension formula should be considered separately, depending upon the theological and physico-chemical re- quirements of the formula. This paper presents a method for evaluating suspension vehicles rele- vant to specific suspension formulas. The method is based on the theo- logical requirements of good suspension vehicles and the factors which influence the selection of the most effective vehicle. Also, a check-list is * Smith Kline and French Laboratories, Pharmaceutical Research Section, Research and Development Division, Philadelphia 1, Pa. 123

124 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS proposed for formulating suspensions with the minimum of phase separa- tion. RHEOLOGICAL REQUIREMENTS From a practical viewpoint, a good suspension vehicle is one which is both "thick" enough to suspend particles and "thin" enough to shake and pour easily. The balancing of these two requirements is difficult and has long been one of the more perplexing problems in the formulation of suspensions. In order to gain a better understanding of the rheological requirements of a good suspension vehicle, the conditions under which the vehicle should be thick and those under which it should be thin will be considered briefly. When a suspension is at rest the particles tend to settle under the influence of gravity. The vehicle, then, should be thick so as to prevent or retard the movement of the particles. When the suspension is shaken and then poured, the vehicle should be thin to permit these operations to be done with ease. We are concerned, therefore, with two conditions in- volving the magnitudes of shearing stress to which the suspension is sub- jected after it is prepared (2, 3): namely (1) the low shearing stresses accompanying the settling of the particles, and (2) the higher shearing stresses caused by shaking and pouring the suspension. The shearing stresses resulting from particle sedimentation are usually of a low order. For small, spherical particles whose density differs only slightly from that of the vehicle, these stresses can be calculated from basic principles. The total force (Fv) of a particle of radius r, volume/7,, and density 0s, suspended in a vehicle of density or, is related to the upward (F•) and downward (Fa) forces acting upon the particle. Hence, Fv = Fd -- F,• = l/•o•g- l/•o•,g (1) or Fv = 4/3 r rg (p, - or) (2) where g is the gravitational constant. In terms of shearing stress (r, the force per unit area), the equation becomes • = '/8 rg (,• - p0 (3) Plots of shearing stress against particle radius for various differences in densities between the particle and vehicle are shown in Fig. 1. It can be seen that for particles usually found in suspension the shearing stresses are small ( 20 dynes/cm.=). Consequently, the rates of shear resulting from the movement of these particles through the vehicle are proportionately small, depending upon the viscosity of the suspension. The higher shearing stresses induced by shaking and pouring the sus- pension may vary markedly. They depend upon the force applied, the