Composite membrane estradiol implant.

The diffusion and permeability of large organic molecules through polymeric films were investigated, specifically the passage of estrogen through films of polyethylene, silicone, or a composite of these two films. Such systems are of interest because of the possibility of constructing a biocompatible implant that releases a hormone at a controlled and desired rate. Diffusion and permeability coefficients through implants of a desirable size-successfully tested in rats-were measured by the "time lag" method of diffusion, and solubility coefficients were determined by the method of sorption kinetics. Independently derived values were in good agreement. An interesting observation was made with implications for the controlled release from membrane-based drug delivery systems. Permeability coefficients of estrogen are orders of magnitude higher when estrogen is present as a solid rather than in a dilute solution, while diffusion coefficients are equal. This finding is explained by the considerably higher partial vapor pressure of estrogen in the former case. In fact, control of the partial vapor pressure of the encapsulated drug is a powerful method for controlling its release rate.