Division of Chemistry and Materials Science, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD 20993, USA.
Acta Biomater. 2011 Feb;7(2):604-13. doi: 10.1016/j.actbio.2010.09.019. Epub 2010 Sep 19.
We have devised a novel diffuse interface formulation to model the development of chemical and physical inhomogeneities, i.e. microstructure, during the process of casting drug-eluting coatings. These inhomogeneities, which depend on the coating constituents and manufacturing conditions, can have a profound affect on the rate and extent of drug release, and therefore the ability of coated medical devices to function successfully. By deriving the model equations in a time-dependent reference frame, we find that it is computationally viable to probe a wide, physically relevant range of material and process quantities. To illustrate the application of the model, we have evaluated the impact of manufacturing solvent, coating thickness and evaporation rate on microstructure development. Our results suggest that modifying these process conditions can have a strong and nearly discontinuous effect on coating microstructure, and therefore on drug release. Further, we demonstrate that the model can be applied to processes that involve the incremental application of the coating in layers or passes. This new model formulation, which can also be used to predict the kinetics of drug release, provides a tool to elucidate and quantify the relationships between process variables, microstructure and performance. Establishing these relationships can reduce empiricism in materials selection and process design, providing a facile and efficient means to tailor the underlying microstructure and achieve a desired drug-release behavior.
我们设计了一种新的弥散界面公式来模拟药物洗脱涂层制造过程中化学和物理不均匀性（即微观结构）的发展。这些不均匀性取决于涂层成分和制造条件，会对药物释放的速度和程度产生深远影响，从而影响涂层医疗器械的成功功能。通过在时变参考系中推导模型方程，我们发现可以计算地探测广泛的、物理相关的材料和工艺数量范围。为了说明模型的应用，我们评估了制造溶剂、涂层厚度和蒸发率对微观结构发展的影响。我们的结果表明，改变这些工艺条件对涂层微观结构（进而对药物释放）有很强的、几乎不连续的影响。此外，我们证明该模型可应用于涉及涂层逐层或逐段递增应用的过程。这种新的模型公式也可用于预测药物释放动力学，为阐明和量化工艺变量、微观结构和性能之间的关系提供了工具。建立这些关系可以减少材料选择和工艺设计中的经验主义，为定制底层微观结构和实现所需的药物释放行为提供了一种简便、高效的方法。
