The solubilities of etoricoxib (ETX), a COX-2 selective nonsteroidal anti-inflammatory drug, were determined in water–ethanol and ethanol–ethyl acetate mixtures at several temperatures (288.15–308.15 K). The solubility curves as a function of ethanol ratio were studied at five temperatures; they showed a single maximum located at 30% ethanol–ethyl acetate (δ 1 = 19.70 MPa 1/2 ). The measurements of the variation of inherent drug solubility with temperature were used to estimate different thermodynamic parameters, enthalpy, entropy and Gibbs energy of solution (Δ H S , Δ S S and $$\Delta G_{{{\text{hm}}}}^{{\text{S}}}$$ Δ G hm S , respectively). The apparent enthalpies of solution were nonlinear functions of the ethanol ratio in aqueous mixture. Non-linear enthalpy–entropy compensation analysis was observed indicating different dissolution mechanisms with the variation in mixture composition. The solubility enhancement is entropy driven in water-rich (0–40% v/v ethanol) and enthalpy controlled in ethanol-rich (40–100% ethanol) compositions, likely due to water structure loss around nonpolar moieties of the drug and in the ethanol rich mixtures it is the enthalpy, probably due to the better drug solvation.

中文翻译：

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两性和两性中依托考昔的热力学分析：几个温度下的非质子溶剂混合物

依托考昔 (ETX)（一种 COX-2 选择性非甾体抗炎药）的溶解度在几种温度 (288.15–308.15 K) 下在水-乙醇和乙醇-乙酸乙酯混合物中测定。在五个温度下研究了作为乙醇比例函数的溶解度曲线；他们显示了一个最大值位于 30% 乙醇-乙酸乙酯 (δ 1 = 19.70 MPa 1/2 )。药物固有溶解度随温度变化的测量值用于估计不同的热力学参数、焓、熵和溶液的吉布斯能（Δ HS 、Δ SS 和 $$\Delta G_{{{\text{hm}}}} ^{{\text{S}}}$$ Δ G hm S ）。溶液的表观焓是含水混合物中乙醇比率的非线性函数。观察到非线性焓-熵补偿分析表明随着混合物组成的变化不同的溶解机制。溶解度的增强是在富水（0-40% v/v 乙醇）中由熵驱动，在富乙醇（40-100% 乙醇）组合物中受焓控制，这可能是由于药物非极性部分周围的水结构损失和富含乙醇的混合物是焓，可能是由于更好的药物溶剂化。