Sá Couto André Rodrigues, Ryzhakov Alexey, Loftsson Thorsteinn
Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavik, Iceland.
Materials (Basel). 2018 Oct 13;11(10):1971. doi: 10.3390/ma11101971.
It is extremely important for pharmaceutical formulators to have analytical methodology that provides efficient detection and quantification of HPβCD aggregates. Five different methods were then evaluated for their potential to detect these aggregates and to determine critical aggregation concentration (cac): osmometry, viscometry, tensiometry, dynamic light scattering (DLS), and permeability studies. Overall, tensiometry was an inadequate method with which to study HPβCD aggregation, since the addition of HPβCD to water resulted in only minor changes in surface tension. Osmolality and viscosity studies have shown that for HPβCD, solute⁻solvent interactions are the main contributors for the observed deviation from ideality. These deviations might be related to the presence of aggregates. The DLS method proved to be an effective method with which to detect HPβCD aggregates and estimate their hydrodynamic diameter, although it presented some limitations concerning their quantification. In terms of the assessed methods, permeation studies were shown to be the best to study HPβCD aggregation phenomena, since they were the only method where the detection of aggregates and the determination of apparent cac values was possible. Also, it was the least invasive for the HPβCD samples and the method that provided more conclusive data. Results suggested that HPβCD, as expected, has less tendency to form aggregates than βCD.
对于药物配方设计师而言，拥有能够有效检测和定量HPβCD聚集体的分析方法极为重要。随后评估了五种不同方法检测这些聚集体以及确定临界聚集浓度（cac）的潜力：渗透压法、粘度测定法、表面张力测定法、动态光散射（DLS）和渗透性研究。总体而言，表面张力测定法是研究HPβCD聚集的不充分方法，因为向水中添加HPβCD只会导致表面张力发生微小变化。渗透压和粘度研究表明，对于HPβCD，溶质 - 溶剂相互作用是观察到的偏离理想状态的主要因素。这些偏差可能与聚集体的存在有关。DLS方法被证明是检测HPβCD聚集体并估计其流体动力学直径的有效方法，尽管在其定量方面存在一些局限性。就所评估的方法而言，渗透研究被证明是研究HPβCD聚集现象的最佳方法，因为它们是唯一能够检测聚集体并确定表观cac值的方法。此外，它对HPβCD样品的侵入性最小，并且该方法提供了更具决定性的数据。结果表明，正如预期的那样，HPβCD形成聚集体的倾向比βCD小。
