Department of Biopharmaceutics and Pharmaceutical Technology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Straße 173, 55216, Ingelheim am Rhein, Germany.
Pharm Res. 2021 Sep;38(9):1549-1561. doi: 10.1007/s11095-021-03096-8. Epub 2021 Sep 27.
A linear solvation energy relationship (LSER) was developed to predict the partitioning of neutral chemicals from polysorbate 80 (PS 80) micelles to water. Predicted partition coefficients were converted to a concentration dependent solubilization strength of aqueous PS 80 solutions. This solubilization strength represents a key parameter to project equilibrium levels of leaching from pharmaceutical plastic materials.
To construct the LSER model equation, partition coefficients between PS 80 micelles and water were measured via a reference phase method or collected from the literature. Multiple linear regression of partition coefficients against five publicly available solute parameters was used to obtain the LSER system parameters.
112 chemically diverse compounds were incorporated for LSER model regression. The model equation shows a very good fit (R = 0.969, SD = 0.219) for the entire dataset. The accuracy of the multi-parameter LSER model was proven to be substantially better in comparison to a single-parameter log-linear model based on the octanol-water partition coefficient.
PS 80 solubilization strength in water can expediently and accurately be calculated for neutral organic compounds with the proposed LSER model. LSER system parameters provide insightful chemical information with respect to solubilization in aqueous solutions of PS 80.
建立了一种线性溶度参数关系（LSER），用于预测中性化学品从聚山梨酯 80（PS 80）胶束到水相的分配。预测的分配系数被转换为水相 PS 80 溶液浓度依赖性的增溶强度。该增溶强度是预测药物塑料材料浸出平衡水平的关键参数。
通过参考相法或文献收集来测量 PS 80 胶束与水之间的分配系数，以构建 LSER 模型方程。通过多元线性回归将分配系数与五个公开的溶质参数进行拟合，以获得 LSER 系统参数。
共纳入了 112 种化学性质多样的化合物进行 LSER 模型回归。该模型方程对整个数据集具有非常好的拟合度（R=0.969，SD=0.219）。与基于正辛醇-水分配系数的单参数对数线性模型相比，多参数 LSER 模型的准确性显著提高。
对于中性有机化合物，可以使用所提出的 LSER 模型方便、准确地计算 PS 80 在水中的增溶强度。LSER 系统参数提供了有关 PS 80 在水溶液中增溶的有价值的化学信息。
