Said A, Makki S, Muret P, Rouland J C, Toubin G, Millet J
Laboratoire de Pharmacie Galénique, Faculté de Médecine et Pharmacie, Besançon, France.
J Pharm Sci. 1996 Apr;85(4):387-92. doi: 10.1021/js950367f.
The aim of this study was to determine and to compare experimental and theoretical solubilities (S) as well as partition coefficients (PC) in an octanol/water system of psoralen (P), 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP) and 4,5',8-trimethylpsoralen (TMP). For each psoralen, experimental results were performed in triplicate with a spectrofluorimetric technique. The measurements were achieved 10 times for each solution. The obtained order of the solubilities in pure octanol was 5-MOP approximately TMP > P > 8-MOP, while in water-saturated octanol it was expressed as follows: TMP approximately 5-MOP > P > 8-MOP. However, the following order was found for hydrophobicity: TMP > 5-MOP > 8-MOP > P. The solubility ratios (SR) in pure octanol and water were assessed (mean +/- SD): 3.13 +/- 0.01 (P), 2.60 +/- 0.01 (8-MOP), 3.75 +/- 0.01 (5-MOP), and 5.11 +/- 0.01 (TMP). In saturated phases, they were 3.27 +/- 0.01, 2.63 +/- 0.01, 3.85 +/- 0.01, and 5.32 +/- 0.01, respectively. The PCs were determined with low concentrations according to the Dearden and Bresnen32 method and they were 1.67 +/- 0.01, 1.93 +/- 0.01, 2.00 +/- 0.01, and 3.14 +/- 0.01, respectively. Solubility parameters (delta), in Hildebrand unit (H) or in (cal/cm3)1/2, were evaluated. They confirmed the polarity of psoralens, previously expressed through the PC, although the positional isomers (5-MOP and 8-MOP) revealed no difference. Hildebrand's approach to the solubility of regular solutions and Yalkowsky's concept of the solubility of nonelectrolytes and weak electrolytes in an octanol/water system permitted a comparison of the theoretical and experimental results. The perspective of this work is to use the physicochemical properties of the psoralens in practice for insuring convenient experimental assays and the prediction, in vitro, of the percutaneous absorption of these compounds.
本研究的目的是测定并比较补骨脂素（P）、8-甲氧基补骨脂素（8-MOP）、5-甲氧基补骨脂素（5-MOP）和4,5',8-三甲基补骨脂素（TMP）在正辛醇/水体系中的实验溶解度（S）和理论溶解度以及分配系数（PC）。对于每种补骨脂素，采用荧光分光光度技术进行了三次重复实验。每种溶液进行了10次测量。在纯正辛醇中获得的溶解度顺序为5-MOP≈TMP＞P＞8-MOP，而在水饱和正辛醇中则如下表示：TMP≈5-MOP＞P＞8-MOP。然而，发现疏水性顺序如下：TMP＞5-MOP＞8-MOP＞P。评估了在纯正辛醇和水中的溶解度比（SR）（平均值±标准差）：3.1±0.01（P）、2.60±0.01（8-MOP）、3.75±0.01（5-MOP）和5.11±0.01（TMP）。在饱和相中，它们分别为3.27±0.01、2.63±0.01、3.85±0.01和5.32±0.01。根据迪尔登和布雷斯南32法在低浓度下测定了分配系数，其分别为1.67±0.01、1.93±0.01、2.00±0.01和3.14±0.01。评估了溶解度参数（δ），单位为希尔德布兰德单位（H）或（cal/cm³）¹/²。它们证实了补骨脂素的极性，此前已通过分配系数表示，尽管位置异构体（5-MOP和8-MOP）没有差异。希尔德布兰德关于正规溶液溶解度的方法以及亚尔科夫斯基关于非电解质和弱电解质在正辛醇/水体系中溶解度的概念允许对理论和实验结果进行比较。这项工作的前景是在实践中利用补骨脂素的物理化学性质，以确保方便的实验分析以及体外预测这些化合物的经皮吸收。
