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Analysis of the burst effect for small molecular weight solutes release from poly(vinyl alcohol) hydrogels.

机译：分析聚乙烯醇水凝胶中释放的小分子量溶质的破裂效应。

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Controlled release of small molecular weight solutes from crosslinked poly(vinyl alcohol) (PVA) hydrogel matrices was investigated. Drugs were loaded at a known concentration during the hydrogel crosslinking procedure. The release profile was characterized by an initial rapid drug release, referred to as “burst effect,” followed by a sustained near-zero-order release. The burst effect was studied under different conditions, such as drug loading concentration, hydrogel crosslinking ratio, drug properties, and polymer aqueous solution concentration; influences of these factors on the burst effect were analyzed. A new parameter, degree of burst (DB) was defined to characterize the relative magnitude of the burst effect compared to the subsequent sustained release. It was found through the experimental studies that no simple design parameter could reduce the burst effect without decreasing the sustained release rate.; Two different techniques, surface extraction and surface preferential crosslinking, were investigated to minimize the burst effect. Both the methods involved changing the system design parameters on a partial basis.; Drug redistribution experiments suggested that the drug migration theory put forth in previous studies to account for the burst effect was not likely applicable in the systems investigated in this project.; A mathematical model based on a diffusion-convection model was studied to simulate the hydrogel swelling and drug release process. The solvent diffusion front velocity, which has been assumed constant in prior studies, was described by an exponential decay equation for the early stage for better simulation of the initial rapid solvent uptake. Since surface desorption of drug molecules is an important factor responsible for the burst effect, a surface desorption boundary condition was applied in the model to replace the perfect sink boundary that has been used in previous studies. According to the results of the drug redistribution experiments, an initial non-uniform drug concentration distribution, with the drug concentrated in the center, was applied and the sustained release stage that followed the burst effect was predicted more accurately. Effects of modeling parameters on the burst effect and the entire release profile were also investigated; results suggested that polymer characteristic relaxation time and the surface desorption constant had significant influences on the burst effect.
机译：研究了交联聚乙烯醇（PVA）水凝胶基质中小分子溶质的控制释放。在水凝胶交联过程中，药物以已知浓度上样。释放曲线的特征是最初的快速药物释放（称为“爆发效应”），然后是持续的接近零级的释放。在不同的条件下研究了突释作用，例如载药量，水凝胶交联比，药物性质和聚合物水溶液浓度。分析了这些因素对爆发效应的影响。定义了一个新的参数，爆裂度（DB），以表征与随后的持续释放相比的爆裂效果的相对大小。通过实验研究发现，没有简单的设计参数可以在不降低持续释放速率的情况下降低爆发效应。研究了两种不同的技术，即表面提取和表面优先交联，以最大程度地减少破裂效应。两种方法都涉及部分更改系统设计参数。药物再分配实验表明，先前研究中提出的用于解释爆发效应的药物迁移理论不太可能适用于本项目研究的系统。研究了基于扩散-对流模型的数学模型，以模拟水凝胶溶胀和药物释放过程。在以前的研究中假设溶剂扩散前沿速度是恒定的，并通过早期的指数衰减方程来描述，以更好地模拟初始快速溶剂吸收。由于药物分子的表面解吸是导致爆发效应的重要因素，因此在模型中应用了表面解吸边界条件，以替代先前研究中使用的理想汇槽边界。根据药物重新分配实验的结果，应用了初始的不均匀药物浓度分布（药物集中在中心），并更准确地预测了爆发效应后的持续释放阶段。还研究了建模参数对爆发效应和整个释放曲线的影响；结果表明，聚合物特征弛豫时间和表面脱附常数对破裂效果有显着影响。

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