Study On The Crystallization Process And Crystal Morphology Of Aspirin

Aspirin,as a common drug,is usually used to antipyretic analgesic,antiinflammatory and antiarthritic.There are dozens of aspirin crystal standards according to the product size.At present,the main problems of domestic manufacturers including the wide size distribution,bad shape and the unstable reproducibility.Therefore,the crystallization and the crystal morphology of aspirin have been systematically studied from the angle of crystallology in this dissertation.In the thermodynamics part,the solubility of aspirin in acetic acid and acetic anhydride mixed solvent is experimentally measured.Modified Apelblat equation and NRTL equation are used to fit the solubility data.Moreover,thermodynamic properties during the dissolution process are calculated through NRTL model.In the nucleation dynamics part,the metastable zone width of aspirin in acetic acid and acetic anhydride mixed solvent is experimentally measured.The factors that effects the metastable zone width are investigated,including the composition of the mixed solvent,saturated temperature and the cooling rate.Modified self-consistent approach and modified 3D classical nucleation theory approach are used to fitted the MSZW.The kinetic parameters and the nucleation parameters are determined.In the study of aspirin morphology,various crystals of different morphologies are cultivated.The effects of crystal temperature and mixed solvent composition on each individual surface are investigated to found how the finally shape is formed.Modified AE model is employed to predict the crystal morphology in the certain solvent.In the end,crystallization process of aspirin is optimized on the fundamental of the studies above.Seed strategy,cooling strategy and composition of the mother liquid are investigated to found its effects on the quality of the final product.Moreover,the best operation condition is determined.