Study On Dilution And Cooling Crystallization Of 11β-Hydroxypregna-1,4,16-triene-3,20-dione

Dexamethasone is a typical corticosteroids drug, which has very important clinical use. It possesses many merits, such as anti-agnail, anti-toxicity, anti-irritability and anti-shock. Nowadays'produce process of 11β-Hydroxypregna-1 , 4 ,16-triene-3,20-dione (one of dexamethasone intermediates) exist some serious problems in yield and quality. Also the product's appearance has obvious shortages. In this thesis the dilution and cooling crystallization process of 11β-Hydroxypregna-1,4,16-triene-3,20-dione was studied systematicly.The 11β-Hydroxypregna-1,4,16-triene-3,20-dione single crystal cultivated by cooling method was analyzed by X-ray single crystal diffraction and its structure was determined.Using the Cerius2 software, the crystal morphology in the vacuum was calculated based on BFDH and AE principle respectively. The influence of temperature on crystal habit was also studied.The solubility of 11β-Hydroxypregna-1,4,16-triene-3,20-dione at different solvent ratio and temperature was determined by dynamic method. The solubility data was regressed in the form ofλh equation. The crystallization metastable zone was also studied by laser method. The thermodynamic data can be used to confirm and improve the crystallization process.Nucleation and growth kinetics were measured by batch-operated methods. The empirical equations for secondary nucleation and crystal growth kinetics were gotten by moment method. A size-independent growth rate model without agglomeration or breakage was established. In adition, the influence of temperature and stir speed on secondary nucleation and crystal growth rate were studied.To obtain high yields and purity, the effects of crystallization conditions (such as the crystallization temperature, seed, addition rate of anti-solvent, stir speed and the final temperature) were investigated in detail, as a result, the relatively better operation technics was found. The method of dilution and cooling crystallization has successfully enhanced the product quality and yield in lab. The product has big size and good crystal habit.The paper supplied the basis for further research and scale up on crystallization of 11β-Hydroxypregna-1,4,16-triene-3,20-dione. There is no similar report to above study result has been published in literature up to date.