Roberts M S, Lai P M, Anissimov Y G
Department of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
Pharm Res. 1998 Oct;15(10):1569-78. doi: 10.1023/a:1011907201096.
An integrated ionic mobility-pore model for epidermal iontophoresis is developed from theoretical considerations using both the free volume and pore restriction forms of the model for a range of solute radii (rj) approaching the pore radii (rp) as well as approximation of the pore restriction form for rj/rp < 0.4. In this model, we defined the determinants for iontophoresis as solute size (defined by MV, MW or radius), solute mobility, solute shape, solute charge, the Debye layer thickness, total current applied solute concentration, fraction ionized, presence of extraneous ions (defined by solvent conductivity), epidermal permselectivity, partitioning rates to account for interaction of unionized and ionized lipophilic solutes with the wall of the pore and electroosmosis.
The ionic mobility-pore model was developed from theoretical considerations to include each of the determinants of iontophoretic transport. The model was then used to reexamine iontophoretic flux conductivity and iontophoretic flux-fraction ionized literature data on the determinants of iontophoretic flux.
The ionic mobility-pore model was found to be consistent with existing experimental data and determinants defining iontophoretic transport. However, the predicted effects of solute size on iontophoresis are more consistent with the pore-restriction than free volume form of the model. A reanalysis of iontophoretic flux-conductivity data confirmed the model's prediction that, in the absence of significant electroosmosis, the reciprocal of flux is linearly related to either donor or receptor solution conductivity. Significant interaction with the pore walls, as described by the model, accounted for the reported pH dependence of the iontophoretic transport for a range of ionizable solutes.
The ionic mobility-pore iontophoretic model developed enables a range of determinants of iontophoresis to be described in a single unifying equation which recognises a range of determinants of iontophoretic flux.
基于理论考量，开发了一种用于表皮离子电渗的综合离子迁移率 - 孔隙模型，该模型使用了溶质半径（rj）接近孔隙半径（rp）时的自由体积和孔隙限制形式的模型，以及rj/rp < 0.4时孔隙限制形式的近似值。在此模型中，我们将离子电渗的决定因素定义为溶质大小（由摩尔体积、分子量或半径定义）、溶质迁移率、溶质形状、溶质电荷、德拜层厚度、施加的总电流、溶质浓度、离子化分数、外来离子的存在（由溶剂电导率定义）、表皮选择透过性、用于解释未离子化和亲脂性离子化溶质与孔隙壁相互作用的分配速率以及电渗作用。
从理论考量出发开发离子迁移率 - 孔隙模型，使其包含离子电渗转运的各个决定因素。然后使用该模型重新审视关于离子电渗通量决定因素的离子电渗通量电导率和离子电渗通量 - 离子化分数的文献数据。
发现离子迁移率 - 孔隙模型与现有的实验数据以及定义离子电渗转运的决定因素一致。然而，溶质大小对离子电渗的预测影响与模型的孔隙限制形式比自由体积形式更一致。对离子电渗通量 - 电导率数据的重新分析证实了模型的预测，即在不存在显著电渗的情况下，通量的倒数与供体或受体溶液电导率呈线性相关。如模型所述，与孔隙壁的显著相互作用解释了一系列可离子化溶质的离子电渗转运所报道的pH依赖性。
所开发的离子迁移率 - 孔隙离子电渗模型能够在一个统一方程中描述一系列离子电渗的决定因素，该方程认识到离子电渗通量的一系列决定因素。
