| Multicomponent solid-liquid phase equilibrium,i.e.dissolution equilibrium or solubility data,is an essential basic data in industrial crystallization,polymorph screening,experimental design and process optimization of new drug development.Especially in the study of crystallization process of organic small molecular compounds,accurate and systematic dissolution equilibrium data plays a vital role.As an important intermediate and biological metabolite,the application of N-acetylglycine covers many fields,such as pharmaceutical industry,chemical industry,biology field,and so on.However,the multivariate solid-liquid equilibrium data of N-acetylglycine reported in the literature are not comprehensive.Therefore,it is necessary to expand the solvent range at different temperatures to determination the multivariate solid-liquid equilibrium data of N-acetylglycine systematically.In this paper,the dissolution equilibrium data of N-acetylglycine in twelve pure solvents including methanol,ethanol,n-propanol,i-propanol,n-butanol,i-butanol,s-butanol,n-pentanol,water,acetone,acetonitrile and 1,4-dioxane,as well as a binary mixed solvent system of methanol+acetonitrile was determined by static gravimetric method from 283.15to 333.15 K.The solubility of N-acetylglycine in twelve pure solvents increased with the increase of temperature,and the solubility was the highest in methanol and the lowest in acetonitrile.The analysis results of pure solvent systems showed that the solubility behavior was influenced by polarity,hydrogen bond,molecular structure,cohesive energy density and other factors.By analyzing the solvation effect of pure solvent systems(KAT-LSER model),it was found that the factors affecting the solubility include the ability of solvent to accept hydrogen bond(?),nonspecific dipolarity/polarizability(?*)and Hildebrand solubility parameter(?H),its contribution accounted for 29.09%,31.83%and 39.08%respectively.In the binary mixed solvent system,when the solvent composition was constant,the solubility of N-acetylglycine increased with the increase of temperature.With the increase of methanol mole fraction,the solubility of N-acetylglycine first increased and then decreased,and the maximum solubility occured when the mole fraction of methanol was 0.900.In the meantime,there was an inflection point in the solubility curve.This phenomenon was called synergistic solvation effect.Hansen solubility parameters were used to correlate and predict the solubility behavior,evaluate the solubility order and miscibility of N-acetylglycine.The modified Apelblat model(ARD=1.856%,RMSD=1.042×10-4),Yaws model(ARD=1.823%,RMSD=1.036×10-4),Jouyban-Acree model(ARD=2.054%,RMSD=1.249×10-4),Machatha model(ARD=2.707%,RMSD=1.734×10-4),Apelblat-Jouyban-Acree model(ARD=2.831%,RMSD=1.572×10-4)and Apelblat-Machatha model(ARD=3.466%,RMSD=2.020×10-4)were used to fit the solubility data.These six models have achieved good fitting results,indicating that could be used to correlate and predict the solubility of N-acetylglycine,and apply to the industrial production process and industrial crystallization process of N-acetylglycine. |
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