SELECTION OF SUSPENDING AGENTS 131 50- 40 I0- 0 • 4 6 I I•- 14 pt-I Figure •.--Effect ofpH upon the yield stress of a Bingham plastic suspension vehicle. TEMPERATURE A good suspension vehicle should not be affected by temperatures normally experienced by suspension products. At high temperatures, i.e., up to 60øC, the vehicle should not become so thin that it permits the particles to settle rapidly. Also, the vehicle should be able to recover its original consistency after being subjected to repeated freeze-thaw cycles. COMPATIBILITY The suspension vehicle should be compatible with every ingredient used in the suspension formula. That is, in addition to the drug(s), it should not be affected by the agents used to sweeten, color and flavor the product or by any other substance in the preparation. C•ECK-L•ST fOR SUSPESS•OS FORMULATIOS This check-list is presented to serve as a guide in the development of suspension products. The step-by-step procedures of the check-list could enable the formulator to exercise better judgment in selecting the

132 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS most suitable suspending agent, and, also, the most effective concentration of the agent for his formula. In doing so, he can minimize the trial and error procedures of suspension formulation. To make full use of the check-list the formulator should have prior knowledge of the physical and chemical properties of the drug he is to suspend. Also, he should be cognizant of the possible effects of the other ingredients in his formula, even though they may be present in small amounts. With this knowledge he will be forewarned of whatever effects each ingredient may have upon the rheological properties of the suspension vehicle. I would like to emphasize that this check-list is based on ex- periences gained with aqueous suspensions. There is reason to believe, however, that it might also apply to non-aqueous suspensions, provided that the same physico-chemical factors, either whole or in part, are inherent in these systems as well. In light of the foregoing discussion the following procedure for formulat- ing suspensions is suggested: 1. Determine the ionic character of the drug (s). 2. Determine the ionic character of each of the other ingredients in the formula. Whenever possible, use nonionic ingredients. 3. Determine the density of the drug and the size of the largest particle to be suspended. On the basis of the information gained from steps 1 to 3, select the sus- pending agent(s) best suited to the formula. Since yield stress is an important and necessary factor in good suspending action, it is advisable, also, to choose the agent with this property. 4. Determine the resulting density of the suspension medium, after incorporating the suspending agent and the bulk ingredients, e.g., sucrose, sorbitol, etc. in the formula. 5. Determine the sedimentation force of the particles. From equation 3. 6. Select the suspending agent and the concentration of the agent on the basis of the yield stress requirements of the formula. In order to prepare a suspension with the minimum of phase separation the yield stress of the vehicle must be in excess of the sedimentation force of the particles. This excess should be sufficient to account for the unpredictable effects as- sociated with concentrated suspension systems. It should also counteract the effects of vibration and temperature variation incurred during transit and storage of the suspension. There is no precise, calculable method by which these effects may be corrected for, but it is possible, quite satis- factorily, to offset them by using several times the required yield stress of the suspension system. 7. drier selecting the suspending agent and establishing the concentration of the agent to be used, formulate the suspension medium. Check the rheological behavior of the medium before adding the powdered drug to