Evaluation, Control, and Prediction of Drug Diffusion Through Polymeric Membranes II: Diffusion of Aminophenones Through Silastic Membranes: A Test of the pH-Partition Hypothesis

Abstract

The steady-state and quasi-steady-state diffusions of 4′-aminopropiophenone, 4′-aminoacetophenone, and 3′-aminoacetophenone through various thicknesses of silastic membrane have been studied as functions of temperature, concentration, pH, and various ethanol–water compositions of diffusing and desorbing solutions. The membranes are impermeable to the protonated compounds, and the pKa values can be obtained from the pH profile of the apparent diffusion constants. The applicability of Fick's law was confirmed and the saturation of the membrane and/or limitations of numbers of binding sites are not rate determining. The transport of drug across the membrane is consistent with the partitioning from the diffusing solution into the membrane, diffusion within the membrane, and subsequent partitioning in the desorbing solution. Equations have been established on the basis of an assumed constancy of an intrinsic diffusion constant within the membrane to predict the transport of drugs through membranes separating different solvents where the drug would have different activities and have been experimentally verified. Satisfactory correlation between the apparent diffusion constants from steady-state diffusion studies and the partition coefficient in chloroform-water solutions has been observed for the several compounds. The apparent diffusion constant of 4′-aminopropiophenone from various ethanol–water solutions is linearly related to the reciprocal of its solubility in these solutions.