Modeling solvent evaporation during the manufacture of controlled drug-release coatings and the impact on release kinetics

J Biomed Mater Res B Appl Biomater. 2009 Aug;90(2):688-99. doi: 10.1002/jbm.b.31336.

Abstract

To improve functionality and performance, controlled drug-release coatings comprised of drug and polymer are integrated with traditional medical devices, e.g., drug eluting stents. Depending on manufacturing conditions, these coatings can exhibit complex microstructures. Previously, a thermodynamically consistent model was developed for microstructure evolution in these systems to establish relationships between process variables, microstructure, and the subsequent release kinetics. Calculations based on the model were, in general, consistent with experimental findings. However, because of assumptions regarding the evaporation of solvent during fabrication, the model was unable to capture variations through the coating thickness that are observed experimentally. Here, a straightforward method is introduced to incorporate solvent evaporation explicitly into the model. Calculations are used to probe the impact of solvent evaporation rate and drug loading on the microstructure that forms during manufacturing and subsequent drug release kinetics. The predicted structures and release kinetics are found to be consistent with experimental observations. Further, the calculations demonstrate that solvent evaporation rate can be as critical to device performance as the amount of drug within the coating. For example, changes of a factor of five in the amount of drug released were observed by modifying the rate of solvent evaporation during manufacturing.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Chemistry, Pharmaceutical / methods
  • Coated Materials, Biocompatible
  • Computer Simulation
  • Delayed-Action Preparations / pharmacology*
  • Drug Delivery Systems*
  • Drug Design
  • Kinetics
  • Microscopy, Confocal / methods
  • Models, Statistical
  • Reproducibility of Results
  • Solvents / chemistry*
  • Tetracycline / administration & dosage
  • Thermodynamics

Substances

  • Anti-Bacterial Agents
  • Coated Materials, Biocompatible
  • Delayed-Action Preparations
  • Solvents
  • Tetracycline