| Crystallization is an important separation and purification process used in many areas such as chemical,pharmaceutical,petrochemical,and biotechnological,as well as electronic industries.Its wide use is due to the highly purified and attractive form in which the compounds can be obtained from relatively impure solutions by means of a single processing step.While crystallization may be carried on from vapor or a melt,the most common industrial method is from a solution.The solvent,solvent content,temperature,agitation and other crystallization parameters can have a great influence on the crystallization process.In this work,the influence of the solvent content on the solubility of D-mannitol and on the polymorphic transformation of N-methyl pyrrolidone(NMP)solvate was investigated.In study 1,solubility behavior of D-man in four mixed solvents from 288.15 K to 318.15 K was studied by both phase equilibria and molecular modelling methods.A dynamic method was employed to determine the data on equilibrium,both molecular dynamic(MD)simulations and density functional theory(DFT)calculations were carried out to reveal the influence mechanism of solvent on solubility behavior.The radial distribution function(RDF)plots indicate that organic solvents have enhancement effect on the water aggregation in solution,and MD results illustrate that the strength in hydrogen bond of solute-organic solvent captures the solubility ranking of D-man in corresponding mixed solvents.Both of them suggest that solubility behavior not only depends on solute-solvent interaction,the solvent-solvent interaction also plays a key role in determining it.The solubility was further fitted using three models and finally,mixing properties(enthalpy,Gibbs energy and entropy)were discussed,indicating the dissolution process is governed by both enthalpy and entropy of solution.In study 2,was reported a unique method for the preparation of aggregated crystals with well-defined shape and size using a solvent penetration-mediated phase transformation.An unusually fast phase transformation of sulfadiazine was observed.The aggregated sulfadiazine crystals are obtained through a water penetration mediated transformation of sulfadiazine N-methyl pyrrolidone solvate.The aggregated particles keep the same shape and size of the parent crystals.In study 3,solution mediated polymorphic transformation of N-methyl pyrrolidone(NMP)solvate into sulfadiazine(SD)was investigated in different contents of N-methyl pyrrolidone(NMP)solvent/water mixtures.The transformations carried out in 30% of NMP solvent mixed with water has driven to the transformation of NMP solvate into needle-on-rhombic-like aggregates crystals of SD as final product,while those carried out in 60%/70% of NMP solvent mixed with water conducted to the transformation of NMP solvate into rod-like single crystals of SD.in order to investigate more about the influence of the solvent content on the transformation process of NMP solvate,additional measurements were done such as determination of the strength of solvent-solvent interactions between the NMP molecules using Molecular simulation(MS),the nucleation rate and the transformation process by the aid of Focused Beam Reactance Measurement(FBRM)and Raman spectrometry,respectively. |
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