Effect of nonionic surfactants on aqueous primidone suspensions.

The following interactions between the soluble surfactant, octoxynol 9, and the very slightly soluble, finely powdered drug, primidone, in aqueous suspension were investigated: adsorption/desorption of the surfactant, micellar solubilization of the drug, and deflocculation of its particles. The last effect, measured by the sedimentation volume of the suspensions, was also investigated for other octoxynols. The adsorption of octoxynol 9 on solid primidone was proportional to the equilibrium surfactant concentration up to the critical micelle concentration. It leveled off at higher concentrations, reaching saturation at completion of a close-packed surfactant monolayer. The adsorption was essentially completely reversible. The solubility of primidone in water was very slight; its micellar solubilization was even less extensive. The sedimentation volume of primidone suspensions decreased with increasing equilibrium concentration of octoxynol 9 and began to level off at the critical micelle concentration of 0.018%. At about twice that concentration, the sedimentation volume became almost constant, but reached its lowest value only at less than or equal to 0.5%. Slow rotation of suspensions prior to sedimentation promoted flocculation and higher sedimentation volumes between 0.01 and 0.03% octoxynol 9. Octoxynols with higher hydrophilic-lipophilic balance than octoxynol 9 produced considerably larger sedimentation volumes at comparable concentrations, due to a lower surface activity and a lesser tendency to adsorb on primidone.