Small Molecule Diffusion and Solubility in Adhesives Used for Transdermal Drug Delivery: Infrared-Attenuated Total Reflectance (IR-ATR) Studies.

Abstract

AbstractA key factor in designing a drug-in-adhesive transdermal drug delivery system is to understand the rate at which the drug and small-molecule excipients can diffuse in the adhesive matrix. The solubility of these components in the adhesive matrix is also of great importance. Results will be presented discussing the use of infrared-attenuated total reflectance (IR-ATR) spectroscopy as a method to measure both diffusion and solubility of small molecules in adhesives. In this method, the donor layer is either a doped adhesive or a free liquid that is placed in contact with a receptor layer which is an undoped adhesive in contact with an IR-ATR crystal. The IR-ATR crystal detects as a function of time any molecules that diffuse from the donor layer into and through the receptor layer.Examples will be discussed of several different experiments that can be performed with this technique. Diffusion coefficients are presented here for testosterone and terpineol in an isooctyl acrylate based adhesive using a doped adhesive donor layer. Diffusion and solubility of liquids in several adhesives has been determined using the experiment where a free liquid is used as the donor. Solubility and diffusion coefficients determined using an oversaturated doped layer containing dispersed, as well as dissolved solute, are presented here for testosterone and for progesterone. Finally diffusion from a doped layer of one adhesive to an undoped layer of a different adhesive was performed as a partition measurement. The parameters that can be extracted from each of these experiments, as well as the limitations of each type of experiment will be discussed.