Thermodynamic dependence of interfacial transfer kinetics of nonionized barbituric acid derivatives in two-phase...

A theory was developed to describe interfacial transport kinetics of a series of drug homologs in a two-phase transfer cell. When tested, the theory held true for 5,5-disubstituted barbituric acid derivatives in a preequilibrated octan-1-ol = (pH 5) aqueous buffer system maintained at 37 degrees and stirred symmetrically at 50 and 100 rpm. Theoretical prediction of transfer kinetics was not possible in such a cell if the phases were stirred asymmetrically. For symmetric stirring, successful prediction of the transfer kinetics of any homolog in the series was possible from a knowledge of the partition coefficient and transfer kinetics of the parent compound, the partition coefficient of the homolog, and some easily determined system variables. The viscosity and density of the two phases and the phase-volume ratio were needed to define a system constant dependent on the solute diffusion coefficient, interfacial area, donor phase volume, and the boundary layer thickness for diffusion in the donor phase volume, and the boundary layer thickness for diffusion in the donor phase. A method is described to enable estimation of this constant from a knowledge of the transfer kinetics of the parent compound. The rank order of compounds in terms of their observed first-order transfer rate constants is shown to be dependent on the characteristics of the solvent system and stirring conditions employed, as well as on the physical chemistry of the solutes. The results are discussed in light of previously documented investigations.