Thermodynamic And Crystal Morphological Studies On The Crystallization Of Glucosamine Hydrochloride

Glucosamine hydrochloride(GAH)is a natural aminohexose,which is widely used in medicine and health care products.At present,the research on GAH is mainly focused on the determination of GAH content,drug stability,formulation and treatment of osteoarthritis,while the research on crystallization thermodynamics and crystal morphology is insufficient.In this thesis,based on the crystallization thermodynamics of GAH,the effects of solvent and crystallization mode on the morphology of GAH were investigated,and the morphology of GAH dendritic crystals was discovered;the growth mechanism of GAH dendritic crystals was studied and elaborated by combining with molecular dynamics simulation.In this thesis,the solubility of GAH in four mixed solvents(methanol+water,ethanol+wwater,isopropanol+water and acetone+water)in the temperature range of 283.15 K～323.15 K was determined by weight method.The data showed that the solubility increased with the increase of temperature and water content.The order of solubility in the binary mixture of solvents was methanol+water>ethanol+water>isopropanol+water>acetone+water when the temperature was constant.A modified Apelblat,van’t Hoff,(CNIBS)/R-K and Jouyban-Acree models were used to correlate the solubility data.Hirshfeld surface analysis was used to reveal the interaction points between GAH molecules,i.e.,the predominance of hydrogen bonding interactions in GAH molecules.Using molecular simulations to study solvent-solvent interactions and solute-solvent interactions in four mixtures,the order of intermolecular interaction forces was:EGAH-methanol>EGAH-ethanol>EGAHisopropanol>EGAH-acetone,which was consistent with the solubility trend.Based on the thermodynamic data,the effects of crystallization methods(evaporation,cooling,solvation and antisolvation crystallization)and solvents on the morphology of GAH crystals were investigated in this thesis.It was found that the crystals of GAH obtained by antisolvation precipitation in isopropanol were dendrites.The effects of parameters such as crystallization temperature,GAH solution concentration,drop acceleration rate,mass ratio of solvent to antisolvent and stirring rate on the morphology of GAH dendrites were further investigated,thus revealing the evolution of GAH dendrites.In this thesis,we investigated the dendrite growth mechanism at the molecular level with the help of molecular simulations.Firstly,the(001),(100),(-100),(020),(0-20)and(1-1-1)crystal planes were identified as the main planes based on the comparison between the experimental crystal morphology and the predicted morphology by molecular simulation.After that,the interaction energies of GAH-water-isopropanol solutions with each crystalline plane of GAH at different supersaturation degrees were simulated and calculated.The results showed that at high supersaturation,the solute accumulates and nucleates at the(001)crystal plane and grows into lamellar crystals,which exhibit branching;the growth rate of the(-100)crystal plane is larger than that of the(100)crystal plane,which exhibits asymmetry between the two sides of the crystal plane;(0-20)the interaction of the crystalline surface with the solute molecules is weak,the surface does not disappear and is the end of the crystal;(020)the crystalline surface grows faster and eventually disappears,manifesting itself as the tip of the surface;(11-1)The crystalline surface area is small,the crystalline surface growth rate is fast,and the crystalline surface disappears.the study of the growth mechanism of GAH dendrites can provide some theoretical basis for the study of the growth of crystal dendritic morphology.