Two-Phase Method for the Investigation of Interphase Transport: I: Theoretical Aspects

As part of a program aimed at the quantitation of factors involved in the oil-water interphase transport of drugs, a two-phase model was theoretically investigated. The model essentially consists of the transport of the drug from an aqueous phase of a given volume across an aqueous diffusion layer of defined thickness, the water-oil interface, and into a lipid sink. Three methods for treating this problem were developed for the one dimensional case. With the assistance of a digital computer the resulting equations were used to compute the effects of a number of variables over a wide range of conditions. The calculations showed that when the oil-water partition coefficient is large, the transport is aqueous diffusion controlled and first-order behavior is followed in the aqueous phase with time. Deviation from first-order behavior occurs when the partition coefficient is low, when the diffusion coefficient in the oil is low, when the diffusion coefficient in the aqueous phase is large, or when the thickness of the aqueous diffusion layer is small. These results are expected to be useful in the design and interpretation of both in vitroand in vivodata on drug transport.