title: Modeling solvent evaporation during the manufacture of controlled drug-release coatings and the impact on release kinetics.
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.
authors.affiliation: Division of Chemistry and Materials Science, Office of Science and Engineering Laboratories, Center for Device and Radiological Health, Food and Drug Administration, Silver Spring, Maryland 20903, USA. chang-soo.kim@fda.hhs.gov
authors.forename: Chang-Soo
authors.initials: CS
authors.lastname: Kim
authors.forename: David M
authors.initials: DM
authors.lastname: Saylor
authors.forename: Martin K
authors.initials: MK
authors.lastname: McDermott
authors.forename: Dinesh V
authors.initials: DV
authors.lastname: Patwardhan
authors.forename: James A
authors.initials: JA
authors.lastname: Warren
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D002626:Chemistry, Pharmaceutical / Q000379:methods; D020099:Coated Materials, Biocompatible; D003198:Computer Simulation; D003692:Delayed-Action Preparations / Q000494:pharmacology*; D016503:Drug Delivery Systems; D015195:Drug Design; D007700:Kinetics; D018613:Microscopy, Confocal / Q000379:methods; D015233:Models, Statistical; D015203:Reproducibility of Results; D012997:Solvents / Q000737:chemistry*; D013752:Tetracycline / Q000008:administration & dosage; D013816:Thermodynamics
chemical_list: D000900:Anti-Bacterial Agents; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D012997:Solvents; D013752:Tetracycline