在 96 孔板中进行的平衡药物溶解度测量显示，在磷酸盐缓冲液 pH6.8 和人肠液中的药物溶解度相似。
Equilibrium drug solubility measurements in 96-well plates reveal similar drug solubilities in phosphate buffer pH 6.8 and human intestinal fluid.
机构信息
Division of Pharmaceutical Technology, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), 00014 University of Helsinki, Finland.
出版信息
Int J Pharm. 2011 Feb 28;405(1-2):132-6. doi: 10.1016/j.ijpharm.2010.12.007. Epub 2010 Dec 10.
This study was conducted to develop a high throughput screening (HTS) method for the assessment of equilibrium solubility of drugs. Solid-state compounds were precipitated from methanol in 96-well plates, in order to eliminate the effect of co-solvent. Solubility of twenty model drugs was analyzed in water and aqueous solutions (pH 1.2 and 6.8) in 96-well plates and in shake-flasks (UV detection). The results obtained with the 96-well plate method correlated well (R(2)=0.93) between the shake-flask and 96-well plates over the wide concentration scale of 0.002-169.2mg/ml. Thereafter, the solubility tests in 96-well plates were performed using fasted state human intestinal fluid (HIF) from duodenum of healthy volunteers. The values of solubility were similar in phosphate buffer solution (pH 6.8) and HIF over the solubility range of 10(2)-10(5)μg/ml. The new 96-well plate method is useful for the screening of equilibrium drug solubility during the drug discovery process and it also allows the use of human intestinal fluid in solubility screening.
本研究旨在开发一种高通量筛选（HTS）方法，用于评估药物的平衡溶解度。采用甲醇在 96 孔板中沉淀固态化合物，以消除共溶剂的影响。在 96 孔板和摇瓶中（UV 检测）分析了 20 种模型药物在水和水溶液（pH 1.2 和 6.8）中的溶解度。在 0.002-169.2mg/ml 的宽浓度范围内，96 孔板法与摇瓶法的结果相关性良好（R(2)=0.93）。此后，使用来自健康志愿者十二指肠的空腹人肠液（HIF）在 96 孔板中进行溶解度测试。在 10(2)-10(5)μg/ml 的溶解度范围内，磷酸盐缓冲溶液（pH 6.8）和 HIF 中的溶解度值相似。新的 96 孔板法可用于药物发现过程中的平衡药物溶解度筛选，并且还允许在溶解度筛选中使用人肠液。
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