Flocculation of suspensions containing nonionic surfactants by sorbitol

Aqueous suspensions of sulfamerazine, salicylamide, and butamben, containing either polysorbate 20 or polysorbate 80 as a wetting agent, were deflocculated. The presence of relatively high concentrations of sorbitol in the suspensions resulted in flocculation due to dehydration of surfactant polyoxyethylene groups (reflected by the cloud point). The critical flocculation concentration of sorbitol was reduced by raising the storage temperature, lowering the surfactant concentration, switching from polysorbate 80 to polysorbate 20, or adding sodium sulfate to the suspension formulation. Both the cloud point and the sorbitol critical flocculation concentration depended on the particular drug that was suspended. Methylparaben lowered the cloud point, suggesting that the choice of preservative could influence the suspension characteristics in certain cases. The various dehydrating influences were additive. By assuming that interparticle repulsion becomes negligible at the cloud point, it was possible to use cloud point curves to estimate the critical flocculation concentration of sorbitol.