Study On The Solid-liquid Phase Equilibrium Of Analgin And Its Intermediates And The Effect Of Analgin On The Water-ethanol Azeotropic Syste

In the fine pharmaceutical production,the purity of the drug must be guaranteed to ensure the effectiveness and safety of the drug.Therefore,the purity requirements of the drug are stipulated in the quality standard of the drug.Impurities in drugs are the main factors that affect the purity.The increase of impurities makes the content of drugs obviously low or the activity is reduced,and the toxic and side effects are significant.In order to ensure the high purity of the product,the separation and purification of material is often used in the industry,in which crystallization is an important means of material separation and purification.The crystallization process is the process of solute precipitation from the solution,but the precipitation at any temperature in which solvent is the key factor affecting the crystallization.In order to study the crystallization process scientifically and effectively,it is particularly important to determine the equilibrium data of the solid and liquid phase of the target material in a variety of solvents at multiple temperatures.In this paper,the solubility of dipyrone,aminoantipyrine and antipyrine in different solvents and at different temperatures is studied.In the process of industrial production,a large amount of impurities are produced in intermediates,the separation of impurities is also made by the various manufacturers,but the effect of is not good.There are a series of questions on the quality of intermediates and final products in the process of production,including the low crystallization rate of dipyrone,the incomplete separation of impurities,and the large amount of mother liquid produced in the process is heavy.The solubility data of the three target substances are obtained.Using the correlation equation to fit the obtained solubility data to get the parameters of the correlation equation,that is to find the inherent law and predict the solubility data of the solute at other temperatures,which can greatly enrich the solid liquid phase equilibrium database of the solute.At the same time,by the equilibrium still method,obtaining relevant data of water ethanol azeotropic system before and after adding some substance.Preliminary experimental results show that dipyrone can enhance the separation efficiency of water-ethanol system.The main experiment was to determine the solubility of dipyrone at nine temperature points(293.15K～332.85K)in water,methanol,ethanol,1-propanol,2-opropanol,1-butanol,2-obutanol,acetone,methyl acetate,ethyl acetate and in water ethanol mixture of different concentrations(0.1～0.9);The solubility of aminoantipyrine at nine temperature points(299.05K～338.35K)in water,ethanol,methanol,2-opropanol,1-propanol,2-obutanol,1-butanol,acetone and ethyl acetate and in nine different concentrations(0.1～0.9)water ethanol mixed solvent;The solubility of antipyrine at nine temperature points(288.15K～328.15K)in water,methanol,ethanol,1-propanol,2-opropanol,1-butanol,2-obutanol,acetone,methyl acetate,ethyl acetate and in water ethanol mixture of different concentrations(0.1～0.9);In this paper,the solubility curves of Amy Amy,4-amidpyrin and antipyrine in pure solvent and mixed solvent are drawn.The change trend and law of solubility can be shown well in the diagram.At the same time,the experiment of X-ray diffraction(XRD)of the three substances was done.The results showed that the structure of the target substance did not change before and after the experiment,and the consistency was good.In order to get the melting enthalpy and melting point of the three target substances,the target substance was characterized by differential scanning calorimetry(DSC),so that the equation could be further used to fit the experimental data.At the same time,the thermodynamic analysis of the dissolving process of the object was also carried out,and the entropy(ΔdSm),enthalpy(ΔdHm),entropy contribution(%ξTS)and enthalpy contribution(%ξH)were obtained.In this paper,five thermodynamic equations,Van’t Hoff、Apelblat、λh、NRTL、Wilson,were used to fit the solubility data of dipyrone,aminoantipyrine and antipyrine in pure solvents.The fitting data included equation fitting value and the equation parameters.According to the average relative deviation between fitted value and laboratory value,The small ARD value indicates that the effect of correlation is good.The fitting results of Apelblat equation for dipyrone is better.The fitting effect of λh equation to aminoantipyrine is better and the fitting effect of Apelblat equation to antipyrine is better.In this paper,six thermodynamic equations,Van’t Hoff、Apelblat、λh、NRTL、Wilson、Jouyban-Van’t Hoff,were used to fit the solubility data of dipyrone,aminoantipyrine and antipyrine in different concentrations(0.1～0.9)Water-ethanol mixed solvents.The fitting data included equation fitting value and the equation parameters.The fitting results of Apelblat equation for dipyrone is better.The fitting effect of λh equation to aminoantipyrine is better and the fitting effect of Wilson equation to antipyrine is better.The data of Gas-liquid phase equilibrium of the experimental group(water-ethanol-dipyrone)and control group(water-ethanol)was determined in this paper,The gas-liquid equilibrium data were processed,and the results showed that the composition of the gas-liquid phase of the water-ethanol system was changed by dipyrone,The equilibrium temperature of the system increased by dipyrone,the activity coefficient of ethanol increased and the activity coefficient of water decreased,dipyrone makes relative volatility of water-ethanol in ethanol high concentration range increased.