Semmling Beatrice, Nagel Stefan, Sternberg Katrin, Weitschies Werner, Seidlitz Anne
Institute of Pharmacy, Center of Drug Absorption and Transport, Ernst-Moritz-Arndt University of Greifswald, Greifswald, Germany.
Institute for Biomedical Engineering, University of Rostock, Rostock, Germany.
Eur J Pharm Biopharm. 2014 Aug;87(3):570-8. doi: 10.1016/j.ejpb.2014.04.010. Epub 2014 May 4.
In vitro drug release testing is an appropriate approach to identify critical parameters helping to predict drug release from drug-eluting stents (DES) prior to studying drug release behavior under in vivo conditions. Drug release and distribution from DES coated with a fluorescent model substance were studied in vitro using the vessel-simulating flow-through cell equipped with different long-term stable hydrogel compartments composed of agarose, polyacrylamide or poly(vinyl alcohol). The obtained experimental results were compared with the results of finite-element modeling obtained using experimentally determined diffusion coefficients and partition coefficients. In spite of differences regarding these parameters, experimental and mathematical data yielded only minor differences between the different gels regarding the release and distribution behavior and reasonable agreement between the modeling and the experiment was obtained. In an attempt to further elucidate the dosage form behavior, the diffusion coefficients in the gel as well as in the stent coating were systematically varied in the finite-element model. Changes in the diffusivity in the stent coating mainly impacted on the initial concentrations. Slower diffusion inside the hydrogel yielded a retarded elution from the stent coating and a higher model substance accumulation in the gel compartment at late time points.
体外药物释放测试是一种合适的方法，有助于在研究体内条件下的药物释放行为之前，确定有助于预测药物洗脱支架（DES）药物释放的关键参数。使用配备有由琼脂糖、聚丙烯酰胺或聚乙烯醇组成的不同长期稳定水凝胶隔室的血管模拟流通池，体外研究了涂有荧光模型物质的DES的药物释放和分布。将获得的实验结果与使用实验确定的扩散系数和分配系数得到的有限元模拟结果进行比较。尽管在这些参数方面存在差异，但实验数据和数学数据在不同凝胶的释放和分布行为方面仅产生了微小差异，并且在建模和实验之间获得了合理的一致性。为了进一步阐明剂型行为，在有限元模型中系统地改变了凝胶以及支架涂层中的扩散系数。支架涂层中扩散率的变化主要影响初始浓度。水凝胶内部较慢的扩散导致从支架涂层的洗脱延迟，并且在后期时间点凝胶隔室中模型物质的积累更高。
