King's College London, Institute of Pharmaceutical Science, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, United Kingdom.
Int J Pharm. 2012 Dec 15;439(1-2):334-41. doi: 10.1016/j.ijpharm.2012.09.001. Epub 2012 Sep 7.
Weak ion-ion interactions, such as those associated with ion-pair formation, are difficult to isolate and characterise in the liquid state, but they have the potential to alter significantly the physicochemical behaviour of molecules in solution. The aim of this work was to gain a better understanding of how ion-ion interactions influenced passive membrane transport. The test system was composed of propylene (PG) glycol, water and diclofenac diethylamine (DDEA). Infrared spectroscopy was employed to determine the nature of the DDEA ion-pair interactions and the drug-vehicle association. Passive transport was assessed using homogeneous synthetic membranes. Solution-state analysis demonstrated that the ion-pair was unperturbed by vehicle composition changes, but the solvent-DDEA interactions were modified. DDEA-PG/water hydrogen bonding influenced the ion-pair solubility (X(dev)) and the solvent interactions slowed transport rate in PG-rich vehicles (0.84±0.05 μg cm(-2) h(-1), at ln(X(dev))=0.57). In water-rich co-solvents, the presence of strong water structuring facilitated a significant increase (p<0.05) in transmembrane penetration rate (e.g. 4.33±0.92 μg cm(-2) h(-1), at ln(X(dev))=-0.13). The data demonstrates that weak ion-ion interactions can result in the embedding of polar entities within a stable solvent complex and spontaneous supramolecular assembly should be considered when interpreting transmembrane transport processes of ionic molecules.
弱离子-离子相互作用，如与离子对形成相关的相互作用，在液态下难以分离和表征，但它们有可能显著改变溶液中分子的物理化学行为。这项工作的目的是更好地了解离子-离子相互作用如何影响被动膜转运。测试系统由丙二醇（PG）、水和双氯芬酸钠二乙胺（DDEA）组成。红外光谱用于确定 DDEA 离子对相互作用和药物-载体的缔合。采用均质合成膜评估被动转运。溶液态分析表明，离子对不受载体组成变化的影响，但溶剂-DDEA 相互作用发生了变化。DDEA-PG/水氢键影响离子对的溶解度（X(dev)），溶剂相互作用使 PG 丰富的溶剂中的转运速率减慢（0.84±0.05 μg cm(-2) h(-1)，ln(X(dev))=0.57）。在富含水的共溶剂中，强水结构的存在显著增加了跨膜渗透速率（例如，ln(X(dev))=-0.13 时，4.33±0.92 μg cm(-2) h(-1)）。数据表明，弱离子-离子相互作用可导致极性实体嵌入稳定的溶剂络合物中，在解释离子分子的跨膜转运过程时应考虑自发的超分子组装。
