过饱和度
溶解度
水溶液
相(物质)
化学
液态液体
化学工程
水溶性
液态水
材料科学
色谱法
有机化学
热力学
物理
工程类
作者
Grace A. Ilevbare,Lynne S. Taylor
摘要
Highly supersaturated aqueous drug solutions are often generated during drug testing and upon delivery to the patient. The phase behavior of such solutions appears complex and poorly understood, with the formation of colloidal drug aggregates often being reported. In this study, the phase behavior of eight hydrophobic poorly water-soluble drug molecules in highly supersaturated aqueous solutions was examined, and colloid formation was explained in terms of liquid–liquid phase separation (LLPS). A relationship was found between the concentration at which LLPS was observed and the theoretically predicted amorphous “solubility” value, where the latter was predicted based on the thermodynamic properties of the crystalline solid/supercooled liquid and solution activity coefficients. A phase diagram for the ritonavir–water system as a function of temperature was used to demonstrate that LLPS occurs in the metastable region of the phase diagram, and thus LLPS is a precursor to crystallization. Using an amorphous...
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