Study On New Technology Of Dexameth- Asone Sodium Phosphate Crystallization

Dexamethasone sodium phosphate is one kind of important drugs of ardrenal cortex hormone, and it is widely used in clinical application. Up to now, home-made dexamethasone sodium phosphate is not as good as those overseas products in terms of its purity and size etc. In this paper, the crystal structure, crystal habit, crystallization thermodynamics, crystallization kinetics and the plant-scale reaction-dilution coupled crystallization technics of dexamethasone sodium phosphate was studied. The manufacturing process with output of 60 ton/year for dexamethasone sodium phosphate was designed and set up. The diffraction data for dexamethasone sodium phosphate crystal was collected by X-ray diffraction technique. Using the indexing program named TREOR90, the unit cell parameters and space group for dexamethasone sodium phosphate were obtained by the indexing of its diffraction data. The effect of crystallization method, solvent and temperature on crystal habit of dexamethasone sodium phosphate were investigated by SEM(scanning electronics microscope) analysis. The solubility of dexamethasone sodium phosphate in different solvents was determined by laser monitor method. The effect of temperature and solvent on solubility was discussed. Crystallization metastable zone of dexamethasone sodium phosphate in methanol-acetone-water system was determined. The empirical model for solubility and metastabel zone of dexamethasone sodium phosphate was gotten by the least square method. The reaction and dilution crystallization kinetics for dexmethasone sodium phosphate were analyzed. The empirical optimum operation schedule for dexamethasone sodium phosphate coupled crystallization process was established by synthetically considering property of crystal production, thermodynamics, kinetics and experimental study results. The manufacturing process for dexamethasone sodium phosphate was successfully designed and industrialized. The quality of the crystal product is as good as overseas product or better. The work about crystal structure and the crystallization new technics for dexamethasone sodium phosphate, which was done in this paper, has not been reported in any literatures.