Study On Crystallization Process And Morphology Of Acetylpyrazine

Crystallization,as a key step of the process of manufacturing crystal product,plays an important role in the purity,morphology and other properties of the crystal product.The crystallization process is divided into several steps,such as nucleation,growth,and ripening.Every step of the crystallization process may affect the quality of the crystals and the efficiency of the crystallization.The crystal size distribution,polymorphism and morphology can affect the solubility,dissolution rate,melting point and bioavailability of crystals.Therefore,it is of great theoretical and practical significance to study the morphology and its key influencing factors.In this work,the single crystal of acetylpyrazine was first prepared by sublimation.The crystals were characterized by polarizing microscope,PXRD,DSC,SXRD and so on.What's more,the crystal habit was predicted by Material Studio.The crystal morphology in different solvents by cooling crystallization was investigated experimentally.The effect of solvent on the crystal morphology was studied.Thermodynamic properties are essential for studying crystallization process.In this work,the solubilities of acetylpyrazine in seven pure solvents and one binary solvent mixture were determined by a dynamic analytic method with temperatures ranging from 268.15 K to 308.15 K under atmospheric conditions.The modified Apelblat model,?h model,CNIBS/R-K model and NRTL model were used for correlation of the solubility.In addition,the relationship between the solubility and solvent polarity was investigated by an Arrhenius equation.Finally,the dissolution thermodynamic properties of acetylpyrazine in different solvents were calculated and discussed based on NRTL model.In addition,the metastable zone widths of acetyl pyrazine with cooling crystallization in different solvents,saturation temperatures and cooling rates were measured by a laser.The relationship between the cooling rate and the widths of the metastable zone were correlated with the Nyvlt equation and the Sangwal equation,respectively.The nucleation kinetic was investigated.The induction times of acetylpyrazine at three different saturation temperatures were measured using a laser.According to the classical nucleation theory,the nucleation kinetic was analyzed.Based on the study above,the cooling crystallization process of acetylpyrazine were investigated.The effects of temperature,cooling rate,solvent,stirring rate and crystal seed on the crystal morphology of the crystals were considered,according to which an optimized manufacturing process was designed.Finally,the crystals with a satisfied particle size,regular morphology and high transparency were obtained...