Solid-Liquid Equilibria of Succinic Acid in Cyclohexanone,Cyclohexanol and Their Mixed Solvents

Solubilities were measured for succinic acid dissolved in cyclohexanone, cyclohexanol and 5 of their mixed solvents at the temperature range from 291. 85 K to 358.37 K using a dynamic method. The solubility data were regressed by λh equation, with,the average absolute relative deviation 3.47%. The binary interaction parameter is 0.306 7 for the mixed solvent of oyolohexanone and cyclohexanol was determined by correlating the experimental solubilities with the modified λh equation. When the binary interaction parameter was determined it can be used to extrapolate the solubilities of succinic acid in mixed solvents of cyclohexanone and cyclohexanol at any proportion.The average absolute relative deviation was 7. 69% by using the modified λh equation to correlate the solubility data, however, the average absolute relative deviation was 8.89% by using NRTL equation to correlate the solubility data. The results show that the accuracy of the modified λh equation is better than that of the NRTL equation for the solubility of succinic acid in the 5 mixed solvents of cyclohexanone and cyclohexanol.

Solubility of β-cyclodextrin in different mixed solvents

The solubility of β-cyclodextrin （β-CD） in ionic liquid/N, N-dimethyl-acetamide （IL/DMAC） mixed solvent and in LiCI/DMAC mixed solvent was investigated at 323.15 K and 353.15 K. The results showed that the solubility of β-CD in IL/DMAC system increased with increasing temperature, but decreased in LiCI/DMAC system. β-CD had the highest solubility in IL/DMAC system with [Cl]- or [Br]- anions. The solubility of β-CD in LiCl/DMAC system was lower than that in IL/DMAC system with [Cl]- or [Br]- anions but higher than that in IL/DMAC system with weak-coordinated anions （e.g [BF4]- or [PF6]-）. The effects of substituent groups （benzyl and butyl） of cation and the structure of cations on β-cyclodextrin solubility were also investigated.

Model evaluation for the prediction of solubility of active pharmaceutical ingredients(APIs) to guide solid–liquid separator design

The assumptions and models for solubility modelling or prediction in systems using nonpolar solvents, or water and complex triterpene and other active pharmaceutical ingredients as solutes aren't well studied. Furthermore, the assumptions concerning heat capacity effects(negligibility, experimental values or approximations) are explored, using non-polar solvents(benzene), or water as reference solvents, for systems with solute melting points in the range of 306–528 K and molecular weights in the range of 90–442 g/mol. New empirical estimation methods for the Δ_(fus)C_(pi) of APIs are presented which correlate the solute molecular masses and van der Waals surface areas with Δ_(fus)C_(pi). Separate empirical parameters were required for oxygenated and non-oxygenated solutes. Subsequently, the predictive capabilities of the various approaches to solubility modelling for complex pharmaceuticals,for which data is limited, are analysed. The solute selection is based on a principal component analysis, considering molecular weights, fusion temperatures, and solubilities in a non-polar solvent, alcohol, and water, where data was available. New NRTL-SAC parameters were determined for selected steroids, by regression. The original UNIFAC, modified UNIFAC(Dortmund), COSMO-RS(OL), and COSMO-SAC activity coefficient predictions are then conducted, based on the availability of group constants and sigma profiles. These are undertaken to assess the predictive capabilities of these models when each assumption concerning heat capacity is employed. The predictive qualities of the models are assessed, based on the mean square deviation and provide guidelines for model selection, and assumptions concerning phase equilibrium, when designing solid–liquid separators for the pharmaceutical industry on process simulation software. The most suitable assumption regarding Δ_(fus)C_(pi) was found to be system specific, with modified UNIFAC(Dortmund) performing well in benzene as a solvent system, while original UNIFAC performs better in aqueous systems.Original UNIFAC outperforms other predictive models tested in the triterpene/steroidal systems,with no significant influence from the assumptions regarding Δ_(fus)C_(pi).

Determination and correlation solubility of 4-nitroimidazole in twelve pure solvents from 278.15 K to 323.15 K

In this paper,the solubility of 4-nitroimidazole in twelve pure solvents(toluene,benzene,1,4-dioxane,acetonitrile,ethyl acetate,acetone,GBL,ethanol,methanol,n-butanol,DMF and NMP)were determined by using the laser monitoring system from 278.15 K to 323.15 K under 101.1 k Pa,which are 0.00018–0.00070,0.00021–0.00073,0.00034–0.00092,0.00038–0.00142,0.00047–0.00120,0.00126–0.00303,0.00225–0.00517,0.00310–0.00724,0.00467–0.00982,0.00453–0.01940,0.01947–0.04652,and 0.04670–0.07452,respectively.At constant temperature,the mole fraction solubility of 4-nitroimidazole were increased as the following order:toluene<benzene<1,4-dioxane<(ethyl acetate or acetonitrile)<acetone<GBL<ethanol<(methanol or nbutanol)<DMF<NMP,and the solubility of 4-nitroimidazole in(ethyl acetate,acetonitrile)and(methanol,n-butanol)had an intersection point at 297.55 K and 281.85 K,respectively.The solubility of 4-nitroimidazole could be increased with increasing temperature in twelve pure solvents.The ideal model,modified Apelblat equation,polynomial empirical equation,andλh equation were used to correlate the experimental values.The experimental solubility values were employed to calculate the standard dissolution enthalpy,standard dissolution entropy and Gibbs energy.The dissolution of 4-nitroimidazole could be an endothermic process in twelve pure solvents.The determination and fitting solubility of 4-nitroimidazole have important guiding significance for the purification and crystallization of its preparation process.

Determination and correlation solubility of m-phenylenediamine in (methanol, ethanol, acetonitrile and water) and their binary solvents from 278.15 K to 313.15 K

In this study, the solubility of m-phenylenediamine in four pure solvents(methanol, ethanol, acetonitrile and water) and three binary solvent(methanol + water),(ethanol + water) and(acetonitrile + water) systems were determined in the temperature ranging from 278.15 K to 313.15 K by using the gravimetric method under atmospheric pressure. In the temperature range of 278.15 K to 313.15 K, the mole fraction solubility values of m-phenylenediamine in water, methanol, ethanol, and acetonitrile are 0.0093–0.1533, 0.1668–0.5589,0.1072–0.5356, and 0.1717–0.6438, respectively. At constant temperature and solvent composition, the mole fraction solubility of o-phenylenediamine in four pure solvents was increased as the following order:water b ethanol b methanol b acetonitrile;and in the three binary solvent mixtures could be ranked as follows:(ethanol + water) b(methanol + water) b(acetonitrile + water). The relationship between the experimental temperature and the solubility of m-phenylenediamine was revealed as follows: the solubility of mphenylenediamine in pure and binary solvents could be increased with the increase of temperature. The experimental values were correlated with the Jouyban–Acree model, van’t Hoff–Jouyban–Acree model, modified Apelblat–Jouyban–Acree model, Sun model and Ma model. The standard dissolution enthalpy, standard dissolution entropy and the Gibbs energy were calculated based on the experimental solubility data. In the binary solvent mixtures, the dissolution of m-phenylenediamine could be an endothermic process. The solubility data,correlation equations and thermodynamic property obtained from this study would be invoked as basic data and models regarding the purification and crystallization process of m-phenylenediamine.

Measurement and Correlation for Solubility of (S)-(+)-2,2-Dimethyl-cyclopropane Carbox Amide in Different Solvents

(S)-(+)-2,2-dimethylcyclopropane carbox amide is a key intermediate of Cilastatin, an inhibitor of de- hydropeptidase-I. Its corresponding solid-liquid equilibrium data will provide essential support for industrial design and further theoretical studies. The solubilities of (S)-(+)-2,2-dimethylcyclopropane carbox amide in toluene, di- chloromethane, trichloromethane, ethyl acetate, ethanol and pure water at different temperature were measured us- ing the synthetic method by a laser monitoring observation technique. The solubility data were correlated with the modified Apelblat equation. The calculated values were good in agreement with the experimental values.

Experimental measurement and thermodynamic modeling of binary and ternary solid–liquid phase equilibrium for the systems formed by L-arabinose,D-xylose and water

Solid–liquid phase equilibrium data for binary(L-arabinose–water) and(D-xylose–water) systems at temperatures from(269.85–298.05) K and ternary(L-arabinose–D-xylose–water) system at temperatures of 273.85 K,278.85 K and 284.45 K were measured at atmospheric pressure.The ternary phase diagrams of the systems were constructed on the base of the measured solubility.Two pure solid phases were formed at given temperatures,including pure L-arabinose and pure D-xylose,which were con firmed and determined by the method of Schreinemakers' wet residue.At the same temperature,the crystallization region of L-arabinose was larger than D-xylose's.The acquired solubility data were then correlated using the NRTL model,Wilson model and Xu model.The calculated solubility with the three models agreed well with the experimental values.

DETERMINATION OF THE SOLUBILITIES OF 2,4-DICHLOROBENZALDEHYDE IN ORGANIC SOLVENTS

Solubilities of 2,4-dichlorobenzaldehyde in five single organic solvents,namely,n-propanol,n-butanol.cyclohexane,chloroform and dichloromethane as well as in two mixed solvents,namely,cyclohexane-acetone and cyclohexane n-butanol,have been measured.These data are correlated withWilson,NRTL and UNIQUAC activity coefficient models and can be used for the process design inthe purification of 2,4-dichlorobenzaldehyde.

Experimental determination of solubilities and＇supersolubilities of 2,2＇,4,4＇,6,6＇-hexanitrostilbene in different organic solvents

The laser monitor technique was used to determine solubilities and supersolubilities of HNS in N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, N-methyl-2-pyrrolidone and 1,4-butyrolactone. The experimental solubility values were correlated with λh equation, modified Apelblat equation and NRTL model. Furthermore, the dissolution enthalpy, dissolution entropy and the Gibbs energy of HNS were calculated by the experimental data. The results show that the solubilities of HNS in the above solvents increase with the increasing temperature. Besides, at the same temperature, the order of solubility is N-methyl-2-pyrrolidone > dimethyl sulfoxide > N,N-dimethylformamide > 1,4-butyrolactone > acetonitrile. The temperature dependence of predicted solubility is in agreement with the experimental data.

Prediction of Solid-Liquid Equilibrium for KCl in Mixed Water-Ethanol Solutions Using the LIQUAC Model

The LIQUAC model is often used to predict vapor-liquid equilibria, osmotic coefficients, and mean ion activity coefficients for electrolyte systems. This paper describes a thermodynamic method to analyze solid-liquid equilibrium for electrolytes in mixed solvents solutions using the LIQUAC model. The KCI solubilities in mixed water-ethanol solutions are predicted with the LIQUAC model and its original interaction parameters. This method is also used to obtain new K^＋-ethanol interaction parameters in the LIQUAC model from the solubility data. The new interaction parameters accurately predict the vapor-liquid equilibrium data of K^＋ salts （including KCI, KBr, and KCOOCH3） in mixed water-ethanol solutions. The results illustrate the flexibility of the LIQUAC model which can predict not only vapor-liquid equilibrium but also solid-liquid equilibrium in mixed solvent systems.

四元体系(NaB_(5)O_(8)+KB_(5)O_(8)+RbB_(5)O_(8)+H_(2)O)288.15 K固液相平衡与相图研究

我国东台吉乃尔盐湖卤水中锂钾硼含量显著,水盐体系相平衡与相图为盐湖矿物的分离提取提供了理论基础。本文对四元体系(NaB_(5)O_(8)+KB_(5)O_(8)+RbB_(5)O_(8)+H_(2)O)在288.15 K时的相平衡与相图采用等温溶解平衡法研究,实验得出溶解度以及平衡液相的密度和折光率这两个主要物化性质,分析且鉴定出存在的盐湖矿物种类。研究发现:288.15 K时,该体系稳定相图中的共饱点(NaB_(5)O_(8)·5H_(2)O+KB_(5)O_(8)·4H_(2)O+RbB_(5)O_(8)·4H_(2)O)的液相组成为w(NaB_(5)O_(8))=9.02%、w(KB_(5)O_(8))=0.47%、w(RbB_(5)O_(8))=0.21%,且3种盐类矿物(NaB_(5)O_(8)·5H_(2)O、KB_(5)O_(8)·4H_(2)O、RbB_(5)O_(8)·4H_(2)O)的体系没有固溶体或复盐生成。三个矿物中RbB_(5)O_(8)·4H_(2)O的结晶区面积最大,溶解度最小。液相的折光率和密度均随Z(NaB_(5)O_(8))的增加呈规律性变化,密度和折光率均采用经验公式进行相对误差计算,所得计算值与实验值吻合较好。

新戊二醇在溶剂中溶解度的测定及关联

用带激光监视系统的可控升温速率的溶解度测定装置,测定了温度范围为286.85－332.75K常压下新戊二醇在有机溶剂甲苯、乙酸丁酯、乙酸乙酯,丙酮、苯、甲苯：异丁醇（3：1体积比）、甲苯：异丁醇（13：2体积比）、异丁醇中的固液相平衡数据。运用λh方程和Apelblat方程对所测物系的溶解度进行了关联,其结果表明溶解度方程在上述的研究温度范围和浓度范围内适用,且λh方程优于Apelblat方程。新戊二醇在溶剂中的溶解度的测定与关联为新戊二醇的工业生产、回收提纯以及理论研究提供了重要的固液相平衡数据。

间苯二甲腈在四种溶剂中溶解度的测定及关联

采用平衡法分别测定了间苯二甲腈在甲醇、甲苯、二甲苯和苯胺四种溶剂中的溶解度,温度范围为293.15~318.15 K,并分别采用λ-h方程、Apelblat模型和Yaws模型对实验数据进行了关联。根据实验数据可以看出间苯二甲腈的溶解度在4种溶剂中均随着温度的升高而升高,并且间苯二甲腈在不同溶剂中的溶解度差别较大。通过4个体系的24个数据点的实验值与计算值相比较,三种模型的总的平均相对误差分别为5.92%、3.90%、3.86%。结果表明λ-h方程、Apelblat模型和Yaws模型都可以较好地关联间苯二甲腈在四种溶剂中的溶解度数据。

枞酸在四种醇类溶剂中的溶解度测定与关联

采用激光监视技术判定平衡点,由动态法测定了枞酸在甲醇、无水乙醇、正丙醇、正丁醇中的固液溶解度,实验测定温度由282 K至320 K,用λh方程、Wilson方程、简化方程分别对溶解度实验数据进行关联。结果表明,枞酸在四种醇类溶剂中的溶解度均随温度的升高而增大,且在不同溶剂中枞酸溶解度有较大的差异,大小顺序为:正丁醇>正丙醇>无水乙醇>甲醇。枞酸在四种醇类溶剂中的溶解度实验数据用λh方程、Wilson方程和简化方程关联的平均相对误差最大值分别为1.43%,1.19%和1.24%。上述结果可为枞酸结晶过程溶剂选择提供基础热力学数据。

牛磺酸在无机盐水溶液中溶解度的测定与关联

用带激光监视系统的可控升温速率的溶解度测定装置,常压下测定了294.07～339.72 K下牛磺酸在硫酸钠、亚硫酸钠水溶液中的固液相平衡数据。并用理想溶液方程、λh方程、Apelblat方程对实验数据进行关联,计算的溶解度与实验值符合良好。运用模型方程对所测物系的溶解度进行了关联,将计算值与实验值进行比较,结果表明理想溶液方程、λh方程、Apelblat方程在所研究的温度范围和浓度范围内是适用的,且Apelblat方程对所研究体系优于λh方程和理想溶液方程。牛磺酸在无机盐水溶剂中的溶解度的测定与关联为牛磺酸的工业生产、分离提纯以及理论研究提供了重要的固液相平衡数据。

固液溶解度实验装置的改进与应用

为了克服传统动态法目测溶解终点给实验测定结果造成的误差,改用激光透过溶液后光强度的变化来判别固液溶解平衡终点。采用灵敏的激光传感器、计算机动态采集温度-时间和光强-时间数据系统,设计组装了激光监视-计算机在线数据采集固液溶解度实验装置。在290～360K下,选取氯化钾–水体系为标准体系,对实验装置进行可靠性检验,结果显示氯化钾在水中溶解度实验值与文献值吻合良好;在280～325K下,使用该装置测定了脱氢枞酸在75%～95%乙醇-水体系中的溶解度,结果表明脱氢枞酸溶解度随温度升高和乙醇浓度增大而增大。

蒽和咔唑在若干有机溶剂中的液固相平衡研究

利用液固相平衡实验装置，测定了蒽和咔唑在二甲基甲酰胺（ＤＭＦ）、Ｎ－甲基吡咯烷酮（ＮＭＰ）、环己酮（ＣＨＮ）、二甲苯、二氯乙烷（ＤＣＥ）和四氯乙烯（ＴＣＥ）中的溶解度，并作出溶解度曲线，为粗蒽的分离和精制提供了有用数据。实验发现ＤＭＦ对粗蒽制取精蒽效果较好，四氯乙烯对粗咔唑的精制效果明显优于传统工艺。

丁二酸在五种有机溶剂中溶解度测定及关联

采用激光监视技术由动态法测定了丁二酸在环己醇、环己酮、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺和冰醋酸中的固液平衡数据,实验测定温度由室温至近353K,并分别用λh方程和NRTL方程对溶解度实验数据进行关联。根据实验数据可以看出丁二酸在五种溶剂中的溶解度均随温度的增加而增大,并且在不同溶剂中丁二酸的溶解度有较大差异。溶解度实验数据用λh方程关联和NRTL方程模型拟合结果的最大平均相对误差分别为3.98%和5.13%。结果表明λh方程模型和NRTL方程模型均能很好地关联丁二酸在五种有机溶剂中的溶解度数据。

氯唑沙宗在不同溶剂中溶解度的测定与关联

氯唑沙宗是一种口服有效的中枢性骨骼肌松弛剂,通过固液相平衡实验可为其合成及纯化工艺中溶剂的选择提供基础数据。采用动态平衡法测定了288.15—318.15 K温度范围内氯唑沙宗在甲醇、乙醇、正丙醇、二氧六环、乙酸乙酯、四氢呋喃和乙腈中的溶解度。结果表明:氯唑沙宗在这7种溶剂中的溶解度均随温度的升高而增大,其中在四氢呋喃中的溶解度最大、乙腈中最小。采用Apelblat方程、λh方程、NRTL和Wilson模型对溶解度数据进行了关联,数据表明实验中的二元体系的关联结果都较好地与实验值相吻合,对比平均相对标准偏差,Wilson模型(平均RSD=0.69%)的关联结果是4种模型中最佳的。

双季戊四醇在3种混合溶剂中的固-液相平衡

采用动态平衡法,在293.15~332.80 K、常压下,测定了双季戊四醇(DPE)在水+(甲醇、乙醇、异丙醇)三种混合溶剂中的溶解度数据。结果表明:DPE在不同质量分数的水+(甲醇、乙醇、异丙醇)混合溶剂中的溶解度随体系温度升高而增大;同一温度下,其在所选取溶剂体系中的溶解度随着甲醇、乙醇或异丙醇质量分数的增大而先增大后减小。λh方程、两参数方程与Apelblat方程均能够对所测定的溶解度数据进行较好的关联;通过修正的van’t Hoff方程计算得到DPE在所选取溶剂体系中ΔsolH0、ΔsolS0和ΔsolG0均大于零,表明DPE在所选取溶剂体系中的溶解过程为吸热、熵增的非自发过程。