Assessment of Drug Diffusion of Sulfathiazole and Metronidazole from Polyurethane Films

Urinary and cardiac catheters, made of polyurethane, are used in patients for extended periods of time. As a result of a catheter’s location and prolonged use, the catheter is vulnerable to contaminants that lead to infections by microorganisms such as Escherichia coli and Candida spp. A polymer that can prevent the development of these microbes, without compromising the functionality of the catheter, would be an ideal solution to this problem. The purpose of this experiment is to develop a polymer that contains an antimicrobial commonly used to treat the various causes of catheter-induced infections.

Polyurethane is the preferred material for catheter production due to its flexibility and biocompatibility with humans, and thus became the material of choice for trials. Sulfathiazole and metronidazole have a history of being prescribed for various infections, including urinary tract infections. While both pharmaceuticals are soluble, metronidazole has a greater ability to dissolve in water. Solubility is an important factor for analyzing the concentration of drug releasing from the polyurethane.

Sample films were made by solvent casting. Polyurethane and the drug (sulfathiazole and metronidazole, separately) were dissolved in a solution of dimethylformamide and tetrahydrofuran. The resultant solution was constantly stirred for 24 hours, after which it was poured into molds, and the molds were placed in an oven at 37°C for 24 hours. The dried films were released from the molds and stored in a desiccator. In order to confirm that drug can diffuse out of the polyurethane, a precisely weighed portion of the drug-loaded polymer film was immersed in distilled water constantly stirred at 200 RPM and 37°C for 8 hours. Every hour, 5 mL aliquot was taken out and tested with a Shimazdu UV-2450 spectrophotometer to measure the absorbance at 270 nm for sulfathiazole and 319.5 nm for metronidazole. The concentrations of aliquots taken out periodically were calculated from the absorbance values and the calibration curve made with standard aqueous solutions of each drug with different concentrations, ranging from 1.25 µg/mL to 100 µg/mL.

Drug-loaded polymer films were made with two different sulfathiazole concentrations, 0.3 wt/wt% and 1.5 wt/wt%. Metronidazole was only made with a 1.5 wt/wt% concentration. Both sulfathiazole concentrations show similar release mechanisms which follow the Korsemeyer-Peppas kinetic model of diffusion; metronidazole follows the same kinetic model. From the similarity in release rates and kinetic modeling, it can be concluded that the diffusion behavior of the medications are independent of its concentration in polyurethane.