Mithani S D, Bakatselou V, TenHoor C N, Dressman J B
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065, USA.
Pharm Res. 1996 Jan;13(1):163-7. doi: 10.1023/a:1016062224568.
The objective of this study was to develop a model to predict the extent to which bile salts can enhance the solubility of a drug, based on the physicochemical properties of the compound. The ability to predict bile salt solubilization of poorly soluble drugs would be a key component in determining which drugs will exhibit fed vs. fasted differences in drug absorption.
A correlation between the logarithm of the octanol/water partition coefficient [log P] of six steroidal compounds and their solubilities in the presence of various concentrations of sodium taurocholate at 37 degrees C, log [SR] = 2.234 + 0.606 log [P] (r2 = 0.987) where SR is the ratio of the stabilization capacity of the bile salt to the solubilization capacity of water for the drug, was used to predict the solubility of the compounds in presence of sodium taurocholate were then measured.
The predicted solubilities were within 10% of the experimentally observed solubilities for griseofulvin, cyclosporin A and pentazocine. The model overpredicted the solubility of phenytoin and diazepam in 15 mM sodium taurocholate solution by a factor of 1.33 and 1.62 respectively.
The expected increase in solubility as a function of bile salt concentration can be estimated on the basis of the partition coefficient and aqueous solubility of the compound.
本研究的目的是基于化合物的物理化学性质开发一个模型，以预测胆盐可增强药物溶解度的程度。预测难溶性药物的胆盐增溶能力将是确定哪些药物在进食与空腹状态下药物吸收存在差异的关键因素。
六种甾体化合物的辛醇/水分配系数的对数[log P]与其在37℃下不同浓度牛磺胆酸钠存在时的溶解度之间的相关性，log [SR] = 2.234 + 0.606 log [P]（r2 = 0.987），其中SR是胆盐对药物的稳定能力与水对药物的增溶能力之比，用于预测化合物在牛磺胆酸钠存在时 的溶解度，然后进行测量。
对于灰黄霉素、环孢素A和喷他佐辛，预测溶解度与实验观察到的溶解度相差在10%以内。该模型分别将苯妥英钠和地西泮在15 mM牛磺胆酸钠溶液中的溶解度高估了1.33倍和1.62倍。
可根据化合物的分配系数和水溶性来估计溶解度随胆盐浓度的预期增加。
