Hänninen Kaisa R, Murtomäki Lasse S, Kaukonen Ann Marie, Hirvonen Jouni T
Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland.
J Pharm Sci. 2007 Jan;96(1):117-31. doi: 10.1002/jps.20729.
The effect of valence of mobile counter-ions (extracting electrolytes), mobile co-ions, and drug-like compounds was evaluated on drug binding/release in ion-exchange fibers. The experimental results support the Donnan theory and suggest that incorporation of monovalent salicylic acid (SA) and divalent 5-hydroxyisophthalic acid (di-COOH) into the anion-exchange fibers was attained mainly as a result of electrostatic (ionic) interaction, with additional contribution of non-electrostatic interactions. Increasing the capacity of ion-exchanger increased the molar amount of compound loading. More efficient release of model anions was observed at increasing valence or concentration of the extracting counter-ion. Potency to release the compounds decreased in the order of citrate (-3) > sulfate (-2) > chloride (-1). The valence of co-ions (sodium (+1) vs. calcium (+2)) in the external solution had only a slight effect on the release. Due to dual site binding (two ionized carboxylate groups), the amount of di-COOH bound into the fibers was half of that of monovalent SA. Also the release was significantly reduced, as the electrostatic interaction was stronger in the case of divalent compound. Simulations on the effect of valence on the Donnan potential and theoretical modeling of the release efficiencies by the external ions supported successfully the conclusions above.
研究了移动抗衡离子（萃取电解质）、移动共离子和类药物化合物的价态对离子交换纤维中药物结合/释放的影响。实验结果支持唐南理论，并表明将单价水杨酸（SA）和二价5-羟基间苯二甲酸（di-COOH）掺入阴离子交换纤维中主要是静电（离子）相互作用的结果，非静电相互作用也有额外贡献。增加离子交换剂的容量会增加化合物负载的摩尔量。在萃取抗衡离子的价态或浓度增加时，观察到模型阴离子的释放更有效。释放化合物的能力按柠檬酸盐（-3）>硫酸盐（-2）>氯化物（-1）的顺序降低。外部溶液中共离子（钠（+1）与钙（+2））的价态对释放只有轻微影响。由于双位点结合（两个离子化的羧基），结合到纤维中的di-COOH量是单价SA的一半。而且释放也显著减少，因为二价化合物的静电相互作用更强。关于价态对唐南电位的影响以及外部离子释放效率的理论模拟成功支持了上述结论。
