Schwartz P A, Rhodes C T, Cooper J W
J Pharm Sci. 1977 Jul;66(7):994-7. doi: 10.1002/jps.2600660724.
The solubility of phenytoin was determined in pH 7.4 and 5.4 phosphate buffers at five temperatures; in hydroalcoholic solutions, 0--4% methanol; and in pH 4.8--8.4 buffer solutions. From the temperature data, the enthalpy and entropy of solution of this nonideal system were calculated and were similar at both pH values. The data obtained from the buffer solutions were used to calculate the apparent dissociation constant, pKa', of phenytoin as 8.06. A GLC method with on-column methylation was used to quantitate phenytoin with 5-(p-methyl-phenyl)-5-phenylhydantoin as an internal standard. The assay uses chloroform of extraction of the drug from aqueous solutions. The ratio of peak heights was adjusted for weights of aqueous and organic layers, and results were calculated in micrograms per gram of sample and mole fraction of phenytoin. Although hydroalcoholic solutions enhanced drug solubility, there is a potentially significant disadvantage in using alcohol for clinical studies.
在五个温度下测定了苯妥英在pH 7.4和5.4的磷酸盐缓冲液中的溶解度；在含0 - 4%甲醇的水醇溶液中以及在pH 4.8 - 8.4的缓冲溶液中的溶解度。根据温度数据，计算了该非理想体系的溶解焓和熵，且在两个pH值下相似。从缓冲溶液获得的数据用于计算苯妥英的表观解离常数pKa'为8.06。采用柱上甲基化的气相色谱法，以5 -（对甲基苯基）- 5 -苯基乙内酰脲为内标物对苯妥英进行定量。该测定法使用氯仿从水溶液中萃取药物。根据水层和有机层的重量对峰高比进行校正，并以每克样品中微克数和苯妥英的摩尔分数计算结果。虽然水醇溶液提高了药物溶解度，但在临床研究中使用乙醇存在潜在的重大缺点。
