Study On The Synthesis And Solid-Liquid Equilibrium Of Zaltoprofen

Zaltoprofen is a non-steroidal anti-inflammatory drug widely used in anti-inflammatory,analgesic and antipyretic,and has good curative effect and safety.However,there are few optimization studies on the synthesis process of zaltoprofen,and there is a lack of solid-liquid phase equilibrium data.Based on this,the synthesis process and solid-liquid equilibrium of Zaltoprofen were studied.The synthesis method of Zaltoprofen was proposed,and the synthesis conditions were optimized,The solid-liquid phase equilibrium data in pure solvent and mixed solvent were determined,and the thermodynamics in the system was studied.The one-step method was used to synthesize zaltoprofen,and the synthesized product was recrystallized and purified by using ethanol and acetic acid as solvent.The synthesized product was synthesized by Fourier transform infrared spectroscopy,high performance liquid chromatography mass spectrometry and DSC&TG.The characterization and analysis of tobuprofen showed that the one-step method successfully synthesized zaltoprofen.The purification effect after recrystallization from acetic acid is better.After purification,the purity of zaltoprofen product is 96.3%,the melting point is 134.1?,and the thermal stability is high and it is not easy to decompose.The single-factor method was used to optimize the synthesis conditions.The optimum conditions were as follows:reaction temperature 80?,reaction time 8 h,phosphoric acid 15 mL,Under this condition,the yield of zaltoprofen product reached 98.61%,;on the basis of single factor method,and using response surface method The synthesis process conditions were further optimized,and the optimized process conditions were:reaction temperature 84.9?,reaction time 8.6 h,phosphoric acid 16.2 mL.Under this condition,the yield of zaltoprofen product reached 97.9%,and the reaction The temperature has a greater influence on the yield of zaltoprofen,followed by the reaction time,and the amount of phosphoric acid in the reaction has a relatively small effect on the yield.The solubility data of zaltoprofen in seventeen pure solvents and two mixed solvents were determined by laser dynamic method.The Apelblat equation,?h equation,ideal equation of state,NRTL equation and Wilson equation were used in pure solvent.The solubility data were fitted.The results show that the above equations have good fitting effect on the solubility data of solute in pure solvent,and the average ARD is lower than 2.04%,but the fitting effect of Wilson equation is better than NRTL equation,Therefore,the activity coefficient in the solution was calculated by the Wilson equation.It was found that the activity coefficients of the studied system were all less than 1,indicating that the solution was positively biased for the ideal solution.The solubility data of zaltoprofen in mixed solvent was correlated by Apelblat equation,ideal state equation and?h equation.The fitting values of all the models agree well with the experimental data,and the Apelblat equation is better than the ideal state equation and?h.The fitting effect of the equation.The solubility of zaltoprofen is as follows:in alcohol solvents,the solubility increases with the polarity of the solvent.In addition,due to the presence of carbonyl and carboxyl groups in zaltoprofen,both acetone,acid and ester The carbonyl group and the carboxyl group are also present,and the higher the similarity with the solvent,the higher the solubility.The solubility in the two mixed solvents increases as the propionic acid mass fraction increases.The thermodynamic parameters including?G^o_sol,?H^o_sol,?S^o_sol,%?_H and%?_TSin the pure solvent and mixed solvent were estimated by the ideal equation of state.The calculation results show that zaltoprofen is selected in the seventeen species.The dissolution process in pure solvent and both mixed solvents is considered to be a endothermic and entropy driven process.The research results of the paper can provide basic data and theoretical basis for the process amplification and engineering design of zaltoprofen,which has important scientific significance and application value.