空气湿度溶解度测定法

Air humidity solubility assay

药物的溶解度数据作为考察药物以及药物制剂的基本参数之一,在药物研发以及相关的工业领域有着重要的意义。现有的溶解度测定基本方法主要有平衡法和动态法等,然而这些传统方法在实际应用中会出现费时费力,样品消耗量大,普遍适用性差等缺点。本文报道了一种测定药物溶解度的新方法——空气湿度法,即采用湿度计测定与药物饱和溶液呈平衡的空气的相对湿度,再用物理化学模型计算出药物的溶解度。以NaCl为模型,在20-50℃内采用新方法测定其溶解度,并与重量分析法测定值及文献报道值进行比较。结果表明空气湿度法测得的溶解度值与重量分析法测定值及文献报道值基本一致。此法测定药物溶解度弥补了现有方法存在的局限性,简便易行,结果可靠,对大多数药物普遍适用。

Measurement of drug solubility is one of the key elements of compound characterization during the drug discovery and development process. A broad variety of solubility assay methods have been developed, including equilibrium method which requires analysis of the equilibrium composition and kinetic method which monitors the concentration of a compound dynamically at the time when a precipitate first appears or disappears in the solution. Despite the numerous experimental methods, precise drug solubility values are hard to obtain for time-consuming, sample size and manual work. In this article, we reported a new method, namely air humidity solubility assay, which measures the relative humidity of the air in equilibrium with the solution at a given temperature, and then calculates solubility from the relative humidity according to extended-non random two liquid （NRTL） model. NaC1 was used as a model drug, and the solubility was measured at the temperature of 20-50 ℃. The results indicate that the solubility of NaC1 determined with the new method is generally comparable to that determined by gravimetry that is reported in literature. The new method has a relative error of less than 2%. Although the accuracy is lower than that of gravimetry, air humidity solubility assay is more convenient, practical, operational and universal. This method provides a supplement to the existing methods.