Avdeef A, Box K J, Comer J E, Hibbert C, Tam K Y
pION Inc., Cambridge, Massachusetts 02138, USA.
Pharm Res. 1998 Feb;15(2):209-15. doi: 10.1023/a:1011954332221.
To investigate a novel approach for the determination of liposomal membrane-water partition coefficients and lipophilicity profiles of ionizable drugs.
The measurements were performed by using a pH-metric technique in a system consisting of dioleylphosphatidylcholine (DOPC) unilamellar vesicles in 0.15 M KCl at 25 degrees C. The DOPC unilamellar vesicle suspension was prepared via an extrusion process.
The liposomal membrane-water partition coefficients of eight ionizable drugs: ibuprofen, diclofenac, 5-phenylvaleric acid, warfarin, propranolol, lidocaine, tetracaine and procaine were determined and the values for neutral and ionized species were found to be in the ranges of approximately 4.5 to 2.4 and 2.6 to 0.8 logarithmic units, respectively.
It has been shown that the liposomal membrane-water partition coefficients as derived from the pH-metric technique are consistent with those obtained from alternative methods such as ultrafiltration and dialysis. It was found that in liposome system, partitioning of the ionized species is significant and is influenced by electrostatic interaction with the membranes. We have demonstrated that the pH-metric technique is an efficient and accurate way to determine the liposomal membrane-water partition coefficients of ionizable substances.
研究一种测定脂质体膜 - 水分配系数以及可电离药物亲脂性分布的新方法。
测量是通过在25℃下由0.15M氯化钾中的二油酰磷脂酰胆碱（DOPC）单层囊泡组成的系统中使用pH测量技术进行的。DOPC单层囊泡悬浮液通过挤压过程制备。
测定了八种可电离药物（布洛芬、双氯芬酸、5 - 苯戊酸、华法林、普萘洛尔、利多卡因、丁卡因和普鲁卡因）的脂质体膜 - 水分配系数，发现中性和离子化形式的值分别在约4.5至2.4和2.6至0.8对数单位范围内。
已表明通过pH测量技术得出的脂质体膜 - 水分配系数与通过超滤和透析等其他方法获得的结果一致。发现在脂质体系统中，离子化形式的分配很显著，并且受到与膜的静电相互作用的影响。我们证明了pH测量技术是测定可电离物质脂质体膜 - 水分配系数的一种有效且准确的方法。
