Study On Azobisisobutyronitrile Crystallization

As an important unit operation,crystallization is widely used as a product separation and purification process in many industrial sectors including chemical,pharmaceutical,and material.For crystalline solid product,in addition to product purity and impurity content,the stability,polymorph,wettability,morphology and size are also important quality measures that need to be controlled.This is because they could have a major impact on the end-use properties of the crystalline product such as a drug's dissolution rate,solubility,and bioavailability as well as on down-stream processing of the solids(e.g.drying,tableting,transport and packing).Although crystallization cannot be regarded as a new process,as a result of its high complexity,there is still a lack of knowledge on the main processes taking place during crystallization.Consequently,the design and optimization of crystallization processes still cannot be fully based on computer simulation,and experiments are still required.In other words,it must go through such a process as from laboratory experiments,to pilot plant trials and to scale-up to industrial production.With the ever-increasing standard on product quality such as on pharmaceutical product quality,international research on crystallization has become even more active today,with attempts to make break-through advances in key aspects.Based on the study on the crystallization process of an organic compound,2,2'-azobis(isobutyronitrile)(AIBN),this work has investigated morphology and size control of crystals as well as primary and secondary nucleation for AIBN.AIBN is an important additive widely used as a former in plastics and rubber and as a radical initiator.Much was discussed in literature on its synthesis processes,but only limited work was reported previously on its crystallization.Poor flowability and caking of AIBN crystal products were reported that seriously affected the end-use.In this study,firstly fully based on experimental study,the crystallization process was studied,and the obtained process condition produced improved size and shape,which led to better flowability and performance in preventing caking.Then the primary and secondary nucleation,as well as modeling and simulation of crystal shape distribution were investigated.The polymorphs,thermodynamics,and metastable zone width(MSZW)in cooling crystallization of AIBN were studied.It confirmed the literature report that AIBN crystals have two polymorphic forms: monoclinic form and triclinic form and monoclinic is the stable form.The solubility of AIBN in methanol,ethanol,benzene,acetone and ethyl acetate solvents and binary solvent of methanol + water at temperatures ranging from 268.15 to 325.15 K were measured.The solubility data were fitted using modified Apelblat model,polynomial equation,and Jouyban-Acree-Van't Hoff model.The MSZW of AIBN in methanol under different temperatures and supersaturations was measured.A model predicting the MSZW of AIBN was established guided by the above data,a process condition was obtained based on seeding that led to square shaped crystals which exhibited improved flowability and performance on preventing caking.In contrast it was found that rod like crystal shape led to caking and poor flowability.For the primary nucleation process of AIBN,the bulk video imaging method was applied.Based on the traditional nucleation theory,the nucleation probability of AIBN in methanol solution was measured.The primary nucleation rate of AIBN at different temperatures and supersaturations was derived.The control step of the primary nucleation process of AIBN was considered as surface diffusion control.Finally,the interfacial energy of the nuclei formed at different temperatures and critical radius,the number of molecules contained in crystal nuclei and critical Gibbs energy of nuclei at different temperature and supersaturation were calculated,which deepen the understanding of primary nucleation process of AIBN.Experiments were designed to measure the facet growth rates of monoclinic crystals under varied temperature and supersaturation(a monoclinic crystal has five independent faces,or in total 14 faces)using stereo-vision imaging technology.Three crystal growth models,i.e.mononuclear growth model?screw dislocation growth model and polynuclear growth model,were employed to derive the relationships between the facet growth rate the supersaturation.The study found that there was less competition between the growth mechanisms of the main surfaces of ABIN crystals.The screw dislocation growth model is the main growth mechanism at low supersaturation and the mononuclear model is the main growth mechanism at high supersaturation.In addition,the effects of flow field state,temperature and supersaturation on crystal growth and crystal morphology were also discussed.Crystal seeding is often used as a measure to avoid the primary nucleation.Secondary nucleation of AIBN in the seeds addition process was studied using 2D imaging technique.The relationship between the average secondary nucleation rate,induction time,final crystal suspension density,agglomeration ratio and initial operation factor were investigated and correlated using several models.The models provide the reference values of the final crystal suspension density,average secondary nucleation rate and induction time in the seeds addition process.A morphological population balance(MPB)model was built using the measured facet growth kinetics.The evolution of crystal morphology and the development of the solution relative supersaturation were explored and the influence of the cooling rate on the crystal morphology was analyzed.The crystal morphology distribution of crystals formed in different cooling rate were predicted and compared to the experimental result,and an acceptable result was obtained.The work took the study on MPB model from the currently computer-based simulation to the next level,i.e.experimental verification and more complicated compounds and crystal structure.