Imboden R, Imanidis G
University of Basel, Switzerland.
Eur J Pharm Biopharm. 1999 Mar;47(2):161-7. doi: 10.1016/s0939-6411(98)00053-8.
The permeation of salbutamol from aqueous vehicles with different pH values through the Celgard 2500 polypropylene membrane was studied, the goal being to assess the effect of the amphoteric properties of the drug on its release by the membrane. Permeation rates were generally low, which was related to the fact that purely aqueous vehicles were not imbibed into the pores of the membrane and therefore permeation took place through the amorphous polypropylene domains. Permeability coefficients were not proportional to the fraction of uncharged drug at different bulk pH values, indicating that either a pH gradient between the bulk and the membrane surface exists and/or charged drug species can permeate the hydrophobic membrane. Calculated hypothetical pH values of the membrane surface, assuming permeation of the uncharged drug only, failed to provide a consistent explanation of the experimental permeabilities. Permeability coefficients of the different ionization forms of the drug assuming no pH gradient were calculated from a system of linear equations, each one of them corresponding to a specific bulk pH. These were for the anionic and the cationic species one to two orders of magnitude smaller than for the combined uncharged and zwitterionic species. It is possible that both, a pH difference between bulk and membrane surface and permeation of ionized molecules were simultaneously responsible for the observed permeation rates.
研究了不同pH值的水性载体中沙丁胺醇透过Celgard 2500聚丙烯膜的渗透情况，目的是评估该药物的两性性质对其通过膜释放的影响。渗透速率通常较低，这与纯水性载体未被膜孔吸收，因此渗透通过无定形聚丙烯区域有关。在不同的本体pH值下，渗透系数与不带电荷药物的比例不成正比，这表明本体与膜表面之间存在pH梯度和/或带电荷的药物种类可以渗透疏水膜。假设仅不带电荷的药物渗透，计算得到的膜表面假设pH值未能对实验渗透率提供一致的解释。从一个线性方程组计算出假设无pH梯度时药物不同电离形式的渗透系数，每个方程对应一个特定的本体pH值。阴离子和阳离子形式的渗透系数比不带电荷和两性离子形式组合的渗透系数小一到两个数量级。本体与膜表面之间的pH差异和离子化分子的渗透可能同时导致了观察到的渗透速率。
