Gelotte K M, Lostritto R T
School of Pharmacy, University of Connecticut, Storrs 06269.
Pharm Res. 1990 May;7(5):523-9. doi: 10.1023/a:1015877002432.
The effect of polar solvents and polar cosolvent mixtures on the transport properties of benzocaine in polydimethylsiloxane (PDMS) was studied. Methanol, ethanol, n-propanol, and n-butanol, as well as aqueous cosolvent mixtures of each n-alkanol, were used as vehicles for benzocaine. A constant activity gradient was maintained in all diffusion studies, with the membrane exposed to saturated donor suspensions of drug, and sink conditions maintained in the receiver. In spite of the constant activity gradient, steady-state benzocaine flux was substantially enhanced with increasing n-alkanol volume fraction and reached a maximum for the pure n-alkanol in each case. At any given composition, the degree of benzocaine flux enhancement generally increased with n-alkanol carbon number. In terms of the appropriate Fick's first law expression for this system, these observations were attributed to simultaneous changes in benzocaine concentration within the PDMS membrane, the diffusion coefficient of benzocaine in PDMS, fillerless membrane volume fraction, tortuosity, and the membrane thickness. These parameters were in turn correlated with the cosolvent composition in contact with the membrane. Both membrane solubility and diffusion coefficient were found to increase substantially, but decreases in tortuosity and increases in fillerless membrane volume fraction and membrane thickness were minor.
研究了极性溶剂和极性共溶剂混合物对苯佐卡因在聚二甲基硅氧烷（PDMS）中传输性质的影响。甲醇、乙醇、正丙醇和正丁醇，以及每种正烷醇的水性共溶剂混合物，被用作苯佐卡因的载体。在所有扩散研究中均保持恒定的活度梯度，使膜暴露于药物的饱和供体悬浮液中，并在接受相中维持漏槽条件。尽管活度梯度恒定，但随着正烷醇体积分数的增加，苯佐卡因的稳态通量显著增强，并且在每种情况下纯正烷醇时达到最大值。在任何给定组成下，苯佐卡因通量增强的程度通常随着正烷醇碳原子数的增加而增加。根据该系统适用的菲克第一定律表达式，这些观察结果归因于PDMS膜内苯佐卡因浓度、苯佐卡因在PDMS中的扩散系数、无填料膜体积分数、曲折度和膜厚度的同时变化。这些参数又与与膜接触的共溶剂组成相关。发现膜溶解度和扩散系数均大幅增加，但曲折度的降低以及无填料膜体积分数和膜厚度的增加较小。
