title: Modeling microstructure development and release kinetics in controlled drug release coatings.
abstract: In recent years, controlled release coatings, comprised of drug-polymer composites, have been integrated with medical devices, improving device functionality and performance. However, relationships between material properties, manufacturing environment, composite (micro)structure, and subsequent release kinetics are not well established. We apply a thermodynamically consistent model to probe the influence of drug-polymer chemistry (phobicity), drug loading, and evaporation rate on microstructure development during fabrication. For these structures, we compute release profiles for exposure to polymer-insoluble media and media in which the polymer readily dissolves. We find that with increasing drug-polymer phobicity, structural heterogeneities form at lower loadings and more rapid rates. The heterogeneities remain isolated and compact at low loadings and become interconnected as the drug to polymer ratio approaches 1.0. Release into polymer-insoluble media was dramatically enhanced by heterogeneities, resulting in up to a fourfold increase in drug release. In polymer-soluble media, however, heterogeneities diminished release. Although reductions of only 30% were typically observed, the absolute changes were much larger than observed in polymer-insoluble media. Our results suggest that improved comprehension and quantification of the physico-chemical properties in controlled release systems will enable the microstructure to be tailored to achieve desired responses that are insensitive to manufacturing variations.
authors.affiliation: Food and Drug Administration, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, Silver Spring, Maryland 20903, USA. david.saylor@fda.hhs.gov
authors.forename: David M
authors.initials: DM
authors.lastname: Saylor
authors.forename: Chang-Soo
authors.initials: CS
authors.lastname: Kim
authors.forename: Dinesh V
authors.initials: DV
authors.lastname: Patwardhan
authors.forename: James A
authors.initials: JA
authors.lastname: Warren
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000493:pharmacokinetics*; D007700:Kinetics; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics; D013499:Surface Properties
chemical_list: D003692:Delayed-Action Preparations; D004364:Pharmaceutical Preparations; D011108:Polymers