Crystal Morphology Modification Of Pronamide From Industrial Crystallization

Crystal habits,the external morphology of the crystalline material,have a direct impact on the follow-up unit operations during chemical process,as well as the apply of crystalline products(dissolution rate,bioavailability etc.).In general,crystal habit is determined by the internal structure characteristics and the external growth environment together.Therefore,it is of great practical and theoretical value to explore the influence mechanism of crystallization factors on particle growth by changing the system conditions.In this paper,Pronamide is picked as a model compound to study its crystallization settings such as solvents,supersaturation and additives,respectively.The details are as follows:The internal non-bond forces are calculated by molecular mechanics calculation,which is based on the data of the pronamide crystal structure analysis.And then,the BFDH and AE model are employed to predict the crystal mor phology under the vacuum condition.In addition,the roughness and bare atoms of anisotropic crystal faces are measured.Furtermore,the modified attachment energy model is used to correct solvent effect,hence the habits are predicted by a nisotropic growth rates.The results show that,with rough and polar surfaces,the crystal faces must take more desorption work with solvents before the new solute molecular(s)transport into the lattice,which significantly reduces the crystal growth rate to result a higher area ratio.The short-rod shaped,double-blade shaped and needle shaped crystals were experimentally screened in the methanol,acetone and toluene respectively,which successfully predicted by the above solvents effect consideration.The effect of supersaturation on the crystal habit is investigated in a single solvent system by establishing a competitive adsorption model containing solvents and solutes.The differences among faces’ growth rate are calculated by measuring ratios of solute and solvent attachment through the study of their diffusion kinetics and adsorption thermodynamics.In this study,the methanol is used to be the solvent surrounding and the crystal growth model is successfully identified to be “2D nucleation & diffusion controlled” mechanism by relating the growth rates with supersaturation and topography testing with AFM.Combined with the crystal anisotropic dissolution rate model,a temperature cycling crystallization process is designed based on super-/under-saturation controlling method,which achieves significant morphology changes.In addition,it is accessible to select the appropriate addition as a tailor additive for blocking the perioidc growth chain,thereby realizing the crystallization control.And in this work,3’,5’-dichloroacetophenone is used appropriately and designedly to block the most powerful bond along the z orientation of a unit cell and reduces the growth of {1 0 2?}.The method,as expected,achieves the block shaped crystals with lower aspect ratio.