Micellar solubilization of barbiturates. I. Solubilities of certain barbiturates in polysorbates of varying hydrophobic chain length.

The effect of the hydrophobic chain length of the non-ionic surfactants, polysorbates, on the degree of solubilization of a series of 5,5-disubstituted barbituric acid derivatives was studied. The solubilities were found to increase as the hydrophobic chain length increases. A pseudo two-phase model, according to which the drug molecule is partitioned between an aqueous phase and a micellar phase, was selected to determine the effect of the chemical structure of the solubilizate on the degree of solubilization. The number of carbon atoms of the substituents on the 5-position, as well as their inductive effects, was found to determine the extent of solubilization.