呋喃唑酮在纯有机溶剂和EDTA二钠盐混合物中的溶剂化动力学: 分子相互作用和热力学见解

doi:10.5246/jcps.2024.10.065

摘要/Abstract

摘要：

增强药物在水中溶解度的基本机制一直是化学家和分析学家感兴趣的课题。此次研究了呋喃唑酮在十二种不同纯溶剂和乙二胺四乙酸二钠(EDTA-2Na)水溶液中的溶解过程。溶解度数据显示, 极性非质子溶剂的溶解度略高于醇和水。值得注意的是, 在EDTA-2Na水溶液中观察到潜溶现象, 呋喃唑酮的溶解度最初随着EDTA-2Na的逐渐加入而增加, 随后降低, 在323.15 K质量分数为0.03时达到最大值(1.949 × 10^–5)。为了阐明溶剂效应, 基于线性溶剂化能关系的概念, 采用Kamlet-Abboud-Taft线性溶剂化能量关系(KAT-LSER)模型。结果表明, 非特异性溶质-溶剂和溶质-溶剂相互作用主要控制呋喃唑酮在这些体系中的溶解。汉森溶解度参数的计算表明, 与其他溶剂相比, 其在DMF和DMAC中的溶解能力更优。同时, 发现局部溶解度参数对整体溶解度参数有显著影响。

关键词: 呋喃唑酮, 溶解度, 潜溶现象, 热力学模型关联

Abstract:

This study systematically examined the dissolution behavior of furazolidone in 12 different pure solvents and in aqueous solutions containing ethylenediaminetetraacetic acid disodium salt (EDTA-2Na). The solubility data indicated that polar aprotic solvents demonstrated a marginally higher solubility of furazolidone compared to alcohols and water. Interestingly, a co-solvency effect was observed in the aqueous solutions of EDTA-2Na, where the solubility of furazolidone initially increased and then decreased with the gradual addition of EDTA-2Na, peaking at a mass fraction of 0.03 (1.949 × 10^–5 at 323.15 K). The analysis using the Kamlet-Abboud-Taft Linear Solvation Energy Relationship (KAT-LSER) model suggested that the dissolution of furazolidone in these systems was predominantly influenced by non-specific solute-solvent and solvent-solvent interactions. Furthermore, Hansen solubility parameter calculations revealed that N,N-dimethylformamide (DMF) and N,N-dimethylacetamide (DMAC) exhibited superior dissolution capabilities compared to other solvents. It was also found that the partial solubility parameters played a crucial role in determining the overall solubility behavior.

Key words: Furazolidone, Solubility, Co-solvency phenomenon, Correlation of thermodynamic models

Supporting: /attached/file/20241104/20241104005827_401.pdf

武宇芳, 郭青枝, 李瑞, 张世琨. 呋喃唑酮在纯有机溶剂和EDTA二钠盐混合物中的溶剂化动力学: 分子相互作用和热力学见解[J]. 中国药学(英文版), 2024, 33(10): 906-917.

Yufang Wu, Qingzhi Guo, Rui Li, Shikun Zhang. Solvation dynamics of furazolidone in pure organic solvents and aqueous EDTA disodium salt mixtures: molecular interactions and thermodynamic insights[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(10): 906-917.

图/表 8

Figure 1. The chemical structure of furazolidone.

Figure 2. The X-ray powder diffraction patterns of solid samples in solution, (a) raw material; (b) DMF; (c) DMAC; (d) 1,4-dioxane; (e) acetonitrile; (f) acetone; (g) ethyl acetate; (h) methanol; (i) ethanol; (j) 1-propanol; (k) 2-propanol; (l) 1-butanol; (m) water; (n) EDTA-2Na aqueous solution, w = 0.01; (o) w = 0.03; (p) w = 0.05; w is the mass fraction of EDTA-2Na in initial solution.

Table 1. Experimental and calculated mole fraction solubility of furazolidone in the solvent at the temperature range from T = (283.15 to 323.15) K under 101.1 kPa.a

Figure 3. The solubility results of furazolidone in pure solvents at different temperatures.

Figure 4. The solubility results of furazolidone in EDTA-2Na aqueous solution at different temperatures, w: the mass fraction of EDTA-2Na in the initial solution.

Table 2. Hildebrand solubility parameters (δH) and solvatochromic parameters α, β, and π* for the selected solvents.a

Table 3. Values of solvents polarity, HSPs of furazolidone, and selected solvents.a

Table 4. The apparent dissolution thermodynamics parameters of furazolidone in pure and mixed solvents at mean harmonic temperature (302.60 K).

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