School of Pharmacy, Queen's University of Belfast, Belfast, Antrim, Northern Ireland, United Kingdom.
School of Pharmacy, Queen's University of Belfast, Belfast, Antrim, Northern Ireland, United Kingdom.
Carbohydr Polym. 2019 Feb 15;206:511-519. doi: 10.1016/j.carbpol.2018.10.072. Epub 2018 Oct 29.
In this study the relationship between the viscoelasticity/mechanical properties of metronidazole-containing aqueous polymer networks composed of HEC and PVP and drug release was statistically modelled. The networks were characterised using oscillatory analysis and drug release was performed using dissolution analysis (pH 7.4). Statistical modelling of the rheological properties and their relationship with drug release was performed using Analysis of Variance, Multivariate Analysis of Variance and stepwise regression. Modelling of drug release was performed using both the Korsmeyer-Peppas and Peppas-Sahlin models to understand the mechanism of drug release and the contributions of network swelling/erosion and diffusion on drug release. HEC and PVP were shown to significantly enhance the rheological properties of the networks. Furthermore, rheological synergy was observed whenever PVP was added to HEC and was due to non-covalent bond formation between these polymers. The magnitude of this synergy increased as functions of increasing concentrations of each polymer. Drug release was dependent on the concentration of HEC and independent of the presence of PVP. The release of metronidazole from networks composed of HEC 3% w/w and PVP (1-5% w/w) was controlled by network swelling/erosion whereas for the networks containing PVP and 5% and 10% w/w HEC, the dominant mechanism of drug release was diffusion. Limited correlation was observed between network rheological properties and drug release. It is suggested that this is due to dissociation of the HEC-PVP interactions and dissolution of PVP during drug release, resulting in a network structure whose properties are dominated by those of HEC. This is the first study that has statistically examined the role of binary polymer network viscoelasticity on drug release. Based on the findings of this study, caution should be shown when formulating aqueous networks with enhanced rheological properties as these effects may not necessarily contribute to other primary determinants of device performance, notably drug release.
在这项研究中，统计模型建立了包含 HEC 和 PVP 的甲硝唑水凝胶的粘弹性/力学性能与药物释放之间的关系。采用振荡分析对网络进行了表征，采用溶出分析（pH7.4）进行了药物释放。采用方差分析、多变量方差分析和逐步回归对流变性能及其与药物释放的关系进行了统计建模。采用 Korsmeyer-Peppas 和 Peppas-Sahlin 模型对药物释放进行了建模，以了解药物释放的机制以及网络溶胀/侵蚀和扩散对药物释放的贡献。HEC 和 PVP 显著增强了网络的流变性能。此外，每当 PVP 添加到 HEC 中时，都会观察到流变协同作用，这是由于这些聚合物之间形成了非共价键。这种协同作用的大小随着每种聚合物浓度的增加而增加。药物释放取决于 HEC 的浓度，与 PVP 的存在无关。由 HEC 3% w/w 和 PVP（1-5% w/w）组成的网络中甲硝唑的释放受网络溶胀/侵蚀控制，而对于含有 PVP 和 5%和 10% w/w HEC 的网络，药物释放的主要机制是扩散。网络流变性能与药物释放之间观察到有限的相关性。据推测，这是由于 HEC-PVP 相互作用的解离和 PVP 在药物释放过程中的溶解，导致网络结构的性质主要由 HEC 决定。这是首次对二元聚合物网络粘弹性对药物释放的作用进行统计学研究的研究。基于这项研究的结果，在配制具有增强流变性能的水凝胶时应谨慎，因为这些影响不一定有助于其他主要决定器械性能的因素，特别是药物释放。
