Small Molecule Diffusion and Solubility in Adhesives Used for Transdermal Drug Delivery: Infrared-Attenuated Total Refle
- PDF / 92,855 Bytes
- 11 Pages / 612 x 792 pts (letter) Page_size
- 5 Downloads / 159 Views
Small Molecule Diffusion and Solubility in Adhesives Used for Transdermal Drug Delivery: Infrared-attenuated Total Reflectance (IR-ATR) Studies. Adam S. Cantor 3M Drug Delivery Systems Division, 3M Center, Building 260-4N-12, St. Paul, MN 551441000, U.S.A. ABSTRACT A 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. INTRODUCTION A factor of great importance in transdermal drug delivery (TDD) systems is the rate at which drug is able to permeate across the skin membrane and enter a patient’s bloodstream. The simplest model description of this delivery process involves two steps. The ability of the drug to move through and out of the transdermal patch, followed by the ability of the drug to permeate through the skin membrane and thus reach the blood circulation. To directly measure drug delivery to the patient, however, requires dosing human subjects with active drugs and taking blood samples. For this reason, most TDD development work relies on simpler in vitro tests to predict delivery performance. The two most common types of in vitro tests are penetration and dissolution tests. Penetration tests are sensitive to both the adhesive matrix and the membrane used (e.g., hairless mouse skin, human cadaver skin). Thus, if a low rate of delivery is measured in a penetration test, it is not clear whether this is due to the adhesive retarding release or if it is due to the membrane retarding permeation of the drug.
NN4.4.1
Dissolution tests measure
Data Loading...
