The Study On The Crystallization Thermodynamic And Crystal Type Of Artemisinin

Artemisinin is one kind of sesquiterpene lactones drugs which contain peroxide groups,and recommended by World Health Organzation(WHO)for treating of malaria for excellent efficicency.Crystallization is the crucial process for manufacturing of artemisinin,for which,purity,crystal form and crystal shape were the important quality indicators,which can affect the down stream operation and qualtity of the finaler product.In this study,after detailed investigation,the systematic research about thermodynamic properties crystal sharp and crytal form were investigated using modern process analytical techniques and advanced molecular simulation method.Firstly,the solubility of artemisinin in acetone-water binary solvent system was measured using gravimetric method,the relationship between solubility of artemisinin with measured temperature and solvent composition was investigated,and the model for prediction of solubility of artemisinin were developed based on selected empirical equation and Apelblat model.Also,the enthalpy of solution for artemisinin in acetone-water binary solvent system was also studied to predict the impact of temperature on the crystallization process.The metastable zone width(MSZW)of artemisinin in acetone-water binary solvent system was measured by using on line turbidimeter,and the relationship between MSZW with process conditions was also investigated and the prediction model was also developed based on least squared method.Then,the crystal shape of artemisinin was simulated using molecular simuation method based on the reported unit cell parameters from Cambridge Crystallographic Database(CCDC),Attachment Energy model(AE)and BFDH model were used to simulate the crystal shape.The impact of attachment energy on growth rate for different crystal facet of was artemisinin also discussed.Finally,the preparation artemisinin whose crystal form is tricline(crystal form VI in these)using anti-sovlent crystllization method was investigated,and the process parameters for preparation of artemisinin with crystal form VI using antisolvent crystallization were optimized subsequently.This study can provide the fundamental data for improving product quality of artemisinin and controlling of the crystal shape and crystal form of artemisinin during anti-sovlent crystllization.