Study On Crystal Habit Regulation Of Nifedipine And Imidacloprid

In the chemical industry,solution crystallization is a traditional technique for the purpose of separation and purification.The different habit of crystal has a significant impact on physical properties such as dissolution rate,packing density and flowability as well as its downstream processing.Controlling strategies of crystal habit include solvent selection,manipulating the supersaturation level,the use of growth additives,temperature cycle,etc.The optimization of appropriate strategy could control crystal habit,and hence improve crystal physical properties and downstream processing efficiency.This work mainly studies the application of different methods in the regulation of crystal habit by using nifedipine and imidacloprid as model compounds.Modification of crystal habit by solvent selection was widely applied;however,the underlying regulation mechanism by solvent was not well-understood.Herein,the effect of solvent on crystal habit and interface assembly of nifedipine(NFD)was investigated by growth experiments in five selected organic solvents of different hydrogen bond affinity properties.It was found that the crystal habit of NFD can be tuned by the hydrogen bond acceptor(HBA)ability of solvent,and the aspect ratio of crystal increases as the HBA ability elevates.Face indexing by single crystal XRD of experimental morphologies,Hirshfeld surface analysis,and surface chemistry of different crystal facets reveal the directionality of solvent interactions with the crystal faces,which is induced by solute-solvent hydrogen bonding interactions.Further,the strength of solute-solvent interactions quantified by adsorption energy calculations and RDF analyses correlates well with the HBA ability of solvents and observed experimental morphology.In all,it was unveiled that the directionality of solute-solvent hydrogen bonding interactions interrupts anisotropically the recognition and assembly of solutes at the crystal-solution interface,resulting in the modification of crystal morphology.By selecting solvents or using additives to optimize crystal habit may be limited because additional separation and purification steps required for engineering solvents or additives may be uneconomical,and adjusting the operating parameters to improve crystal habit is another feasible option.Crystals of imidacloprid from cooling crystallization are thin needles with an aspect ratio of ＞ 10,and the needle-like morphology is not preferred for the downstream processing.The causes of these needlelike crystals include uncontrolled nucleation and the difference in the growth rate of the crystal faces.The effects of the cooling profile,mixing performance and seeding parameters e.g.seeds loading amount,seeding timing and seed type on the aspect ratio of imidacloprid were studied.The results show that the seed type is the key to control the crystal habit of imidacloprid.Herein the method of recrystallization with pure solvent and sonification assistance was introduced to prepare some large seed crystals with decreased aspect ratio.At last,the nucleation and crystal growth were successfully controlled,the plate-like crystals with aspect ratio ＜ 6 were achieved,and the packing density and flowability of products were improved.