Department of Science and Environment, Roskilde University, Roskilde, Denmark.
Department of Science and Environment, Roskilde University, Roskilde, Denmark; Drug Product Development, Janssen Research and Development, Johnson & Johnson, Beerse, Belgium.
J Pharm Sci. 2021 Jul;110(7):2661-2668. doi: 10.1016/j.xphs.2021.02.012. Epub 2021 Feb 17.
The effect of 11 buffers as well as the effect of ionic strength were investigated on the binding between the bile salt taurochenodeoxycholate and the ionic sulfobutylether-β-cyclodextrin. The investigations showed that both ionic strength and competitive binding affected the stability constant. The stability constant for the sulfobutylether-β-cyclodextrin complex increased from 34,400 M to 114,000 M as the ionic strength of the solution increased to 0.15 M. Keeping the ionic strength constant, the stability constant for the complex depended on the buffer in the solution, with citric and succinic acid reducing the stability constant. The reduction in the stability constant by buffers was related to a competitive mechanism. The results showed that, when accounting for the variation in ionic strength between the buffers, three groupings of buffers existed. All carboxylic acid buffers decreased the stability constant of the sulfobutylether-β-cyclodextrin complex, relative to the effect observed by altering the ionic strength, whereas the other buffers only affected the stability constant in terms of the changes in ionic strength. Both buffer species and ionic strength impacted the stability of ionic cyclodextrin complexes, hence, it is important to be aware of these effects when working with, comparing and reporting stability constants.
研究了 11 种缓冲液以及离子强度对牛磺胆酸钠与离子型磺丁基醚-β-环糊精之间结合的影响。研究表明，离子强度和竞争结合都影响稳定常数。随着溶液离子强度增加到 0.15 M，磺丁基醚-β-环糊精配合物的稳定常数从 34400 M 增加到 114000 M。在保持离子强度不变的情况下，配合物的稳定常数取决于溶液中的缓冲液，柠檬酸和琥珀酸降低了稳定常数。缓冲液对稳定常数的降低与竞争机制有关。结果表明，当考虑缓冲液之间的离子强度变化时，存在三组缓冲液。与改变离子强度观察到的效果相比，所有羧酸缓冲液都降低了磺丁基醚-β-环糊精配合物的稳定常数，而其他缓冲液仅根据离子强度的变化影响稳定常数。缓冲液种类和离子强度都影响离子环糊精配合物的稳定性，因此，在使用、比较和报告稳定常数时，了解这些影响很重要。
